glycogen and Diabetes-Mellitus

Liver glycogen α particles are molecularly fragile in diabetic mice, and readily form smaller β particles, which degrade more rapidly to glucose. This effect is well associated with the loss of blood-glucose homeostasis in diabetes. The biological mechanism of such fragility is still unknown; therefore, there are perceived opportunities that could eventually lead to new means to manage type 2 diabetes. The hierarchical structures of glycogen particles are controlled by the underlying biosynthesis/degradation process that involves various enzymes, including, for example, glycogen synthase (GS) and glycogen-branching enzyme (GBE). Recent studies have shown that fragile glycogen α particles in diabetic mice have longer chains and a higher molecular density compared to wild-type mice, indicating an enhanced enzymatic activity ratio of GS to GBE in diabetes. Furthermore, it has been shown that with an improved blood glucose homeostasis, the glycogen fragility in diabetic mice can be restored by treatment with active ingredients from traditional Chinese medicine, yet the underlying mechanism is unknown. In this review, we summarize recent advances in understandings glycogen fragility from the perspectives of glycogen biosynthesis/degradation, glycogen hierarchical structures, and its relation to diabetes. Importantly, we for the first time set GS/GBE activity ratio as the therapeutic target for diabetes.

Topics: Animals; Diabetes Mellitus; Drug Delivery Systems; Glucose; Glycogen; Humans; Hypoglycemic Agents; Liver

Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.

Topics: Animals; Astrocytes; Biological Transport; Blood-Brain Barrier; Brain; Citric Acid Cycle; Diabetes Mellitus; Diabetes Mellitus, Experimental; Energy Metabolism; Glucose; Glutamic Acid; Glutamine; Glycogen; Glycolysis; Humans; Lactates; Models, Biological; Models, Neurological; Neurons; Rats

Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis.

Topics: Adipose Tissue; Altitude; Diabetes Mellitus; Glucagon; Glucose; Glycogen; Homeostasis; Humans; Hyperinsulinism; Hypoglycemia; Hypoxia; Liver; Muscle, Skeletal; Obesity; Time Factors

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

Topics: Animals; Astrocytes; Biological Transport; Brain; Cerebrovascular Circulation; Citric Acid Cycle; Diabetes Mellitus; Energy Metabolism; Glutamic Acid; Glycogen; Glycolysis; Humans; Hypoglycemia; Lactic Acid; Neurons; Potassium; Synaptic Transmission

Skeletal muscle is the largest organ in the body and contributes to innumerable aspects of organismal biology. Muscle dysfunction engenders numerous diseases, including diabetes, cachexia, and sarcopenia. At the same time, skeletal muscle is also the main engine of exercise, one of the most efficacious interventions for prevention and treatment of a wide variety of diseases. The transcriptional coactivator PGC-1α has emerged as a key driver of metabolic programming in skeletal muscle, both in health and in disease. We review here the many aspects of PGC-1α function in skeletal muscle, with a focus on recent developments.

Topics: Aging; Animals; Caloric Restriction; Diabetes Mellitus; Exercise; Glycogen; Humans; Lipid Metabolism; Mice; Muscle, Skeletal; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Transcription Factors

Glycogen phosphorylase (GP) is the enzyme responsible for the synthesis of glucose-1-phosphate, the source of energy for muscles and the rest of the body. The binding of different ligands in catalytic or allosteric sites assures activation and deactivation of the enzyme. A description of the regulation mechanism and the implications in glycogen metabolism are given.. Deregulation of GP has been observed in diseases such as diabetes mellitus or cancers. Therefore, it appears as an attractive therapeutic target for the treatment of such pathologies. Numbers of inhibitors have been published in academic literature or patented in the last two decades. This review presents the main patent claims published between 2008 and 2012.. Good inhibitors with interesting IC50 and in vivo results are presented. However, such therapeutic strategy raises questions and some answers are proposed to bring new insights in the field.

Topics: Animals; Diabetes Mellitus; Drug Design; Enzyme Inhibitors; Glucosephosphates; Glycogen; Glycogen Phosphorylase; Humans; Inhibitory Concentration 50; Molecular Targeted Therapy; Neoplasms; Patents as Topic

While it has long been known that zinc (Zn) is crucial for the proper growth and maintenance of normal biological functions, Zn has also been shown to exert insulin-mimetic and anti-diabetic effects. These insulin-like properties have been demonstrated in isolated cells, tissues, and different animal models of type 1 and type 2 diabetes. Zn treatment has been found to improve carbohydrate and lipid metabolism in rodent models of diabetes. In isolated cells, it enhances glucose transport, glycogen and lipid synthesis, and inhibits gluconeogenesis and lipolysis. The molecular mechanism responsible for the insulin-like effects of Zn compounds involves the activation of several key components of the insulin signaling pathways, which include the extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B/Akt (PKB/Akt) pathways. However, the precise molecular mechanisms by which Zn triggers the activation of these pathways remain to be clarified. In this review, we provide a brief history of zinc, and an overview of its insulin-mimetic and anti-diabetic effects, as well as the potential mechanisms by which zinc exerts these effects.

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Models, Animal; ErbB Receptors; Glycogen; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipogenesis; Receptor, IGF Type 1; Signal Transduction; Zinc; Zinc Compounds

Fibroblast growth factor 19 (FGF19) is a postprandial hormone released from the small intestine. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. This review summarizes the recent advances in our understanding of the biology of FGF19 and its role in glucose homeostasis, with emphasis on publications from 2010 to 2012.. Protein engineering was used to generate FGF19 protein variants that allowed the separation of its mitogenic and metabolic functions. Its cognate receptor in the liver (FGFR4) mediated the effects of FGF19 on proliferation and bile salt synthesis, while this receptor was dispensable for its effects on glucose homeostasis. New metabolic activities of FGF19 were uncovered. FGF19 signaling was shown to stimulate glycogen and protein synthesis, and inhibit gluconeogenesis. FGF19 employed signaling routes distinct from those used by insulin to regulate these pathways. Mice with genetic disruption of Fgf15 (the mouse FGF19 ortholog) were glucose intolerant but had normal insulin levels and normal insulin sensitivity. Reduced hepatic glycogen stores and elevated hepatic gluconeogenesis were observed in the knock-out mice under the conditions in which insulin signaling was active.. FGF19 signaling regulates glucose homeostasis in mice. The (patho)physiological role of FGF19 in glucose homeostasis in humans remains to be determined. Its novel insulin-mimetic actions, combined with the elimination of its mitogenic activity by protein engineering, make FGF19 an attractive candidate for the treatment of type 2 diabetes.

Topics: Animals; Bile Acids and Salts; Blood Glucose; Diabetes Mellitus; Fibroblast Growth Factors; Gastrointestinal Hormones; Gluconeogenesis; Glucose Intolerance; Glycogen; Homeostasis; Humans; Insulin; Insulin Resistance; Liver; Protein Biosynthesis

A large number of compounds mimicking the structures of monosaccharides or oligosaccharides have been discovered from natural sources. Such sugar mimics inhibit carbohydrate-degrading enzymes because of a structural resemblance to the sugar moiety of the natural substrate. Carbohydrate-degrading enzymes are involved in a wide range of important biological processes, such as intestinal digestion, posttranslational processing of the sugar chain of glycoproteins, their quality control mechanisms, lysosomal catabolism of glycoconjugates, and some viral infections. It has now been realized that inhibitors of the enzymes have enormous therapeutic potential in diabetes and lysosomal storage disorders. In this review, the general bioactivity, current applications, and the prospects for new therapeutic applications are described.

Topics: Animals; Binding, Competitive; Carbohydrate Metabolism; Diabetes Mellitus; Enzyme Inhibitors; Glycogen; Glycoside Hydrolases; Humans; Lysosomal Storage Diseases; Mice; Monosaccharides; Protein Folding; Rabbits; Rats

Hepatic-directed vesicle insulin (HDV-I), a novel investigational vesicle (<150 nm diameter) insulin delivery system that carries insulin and a specific hepatocyte-targeting molecule (HTM) in its phospholipid bilayer and has the ability to mimic a portal vein insulin infusion remotely [subcutaneous (SC) HDV-I] and noninvasively (oral HDV-I), has been developed. This review summarizes formulation development, subsequent refinements, and results of preclinical evaluation studies, including biodistribution, mechanistic, and toxicology studies of predominantly SC HDV-I, in various animal models. Studies conducted to date have confirmed the hepatocyte specificity of HDV and HDV-I and revealed that HDV-I can stimulate the conversion of hepatic glucose output to uptake at a dose that is <1% of the dose of regular insulin (RI) required for liver stimulation; suggest that the enhanced antihyperglycemic effect of HDV-I is due to hepatic glucose uptake; and in pancreatectomized dogs during an oral glucose tolerance test, HDV-I normalized blood glucose curves when compared to control curves in intact dogs and prevented secondary hypoglycemia in contrast to the same dose of RI. A 28-day SC HDV toxicity study in rats revealed no clinical, clinical laboratory, or histopathological findings, and the battery of three genetic toxicology studies was negative. Results support the hypothesis that HDV-I works by stimulating hepatic glucose uptake and/or glycogen storage in insulin-deficient animals. The ability to target the delivery of HDV-I to the liver reestablishes the liver as a major metabolic modulator of glucose metabolism. The future of HDV-I depends on the results of ongoing development and longer term clinical trials.

Topics: Administration, Oral; Animals; Biological Transport; Blood Glucose; Chemistry, Pharmaceutical; Diabetes Mellitus; Disease Models, Animal; Dogs; Drug Carriers; Drug Evaluation, Preclinical; Glycogen; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Liposomes; Liver; Mice; Phospholipids; Rats

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase, originally identified as a protein kinase by its ability to phosphorylate and inactivate glycogen synthase. It was found that the overexpression of GSK-3 is associated with some diseases, such as diabetes, Alzheimer disease and other neurodegenerative diseases. Some pharmacological inhibitors of GSK-3 have been demonstrated to mimic insulin signaling, adjust glycogen synthesis and glucose metabolism, and improve insulin resistance. So GSK-3 inhibitors are realized as a new approach of treating diabetes. This review summarizes current advances in research of GSK-3 inhibitors as a new therapeutic approach for diabetes.

Topics: Alzheimer Disease; Animals; Blood Glucose; Diabetes Mellitus; Enzyme Inhibitors; Glycogen; Glycogen Synthase Kinase 3; Humans; Insulin; Insulin Resistance; Signal Transduction

Topics: Chronic Disease; Diabetes Mellitus; Diagnosis, Differential; Enzyme Inhibitors; Exercise Therapy; Glucose; Glycogen; Glycoside Hydrolase Inhibitors; Humans; Liver Diseases; Nutrition Therapy

Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.

Topics: Animals; Biological Transport; Blood Glucose; Diabetes Mellitus; Glycogen; Humans; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Models, Biological; Rats; Vanadium Compounds

Topics: Amino Acids; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Energy Metabolism; Fasting; Gluconeogenesis; Glucose Intolerance; Glycated Hemoglobin; Glycogen; Humans; Lipid Metabolism; Liver; Risk

Topics: Biomarkers; Diabetes Mellitus; Diagnostic Techniques, Endocrine; Glycogen; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulin-Secreting Cells; Lipid Metabolism; Phosphatidylinositol 3-Kinases; Phosphoproteins; Phosphorylation; Polymorphism, Genetic; RNA; Signal Transduction; Specimen Handling

The brain uses glucose as its primary fuel. Cerebral metabolism of glucose requires transport through the blood-brain barrier, glycolytic conversion to pyruvate, metabolism via the tricarboxylic acid cycle and ultimately oxidation to carbon dioxide and water for full provision of adenosine triphosphate (ATP) and its high-energy equivalents. When deprived of glucose, the brain becomes dysfunctional or can be even permanently damaged. Glucose is stored as glycogen within astrocytes with potential importance for tolerance of hypoglycemia. Glycogen may also be important for the metabolic response to somatosensory stimulation and coupling of blood flow and cellular metabolism. Uncontrolled diabetes has a variety of adverse effects upon brain metabolism and function. Many aspects of function that affect the brain may be indirectly linked to cerebral glucose metabolism. Neurotransmitter metabolism, cerebral blood flow, blood-brain barrier and microvascular function may all be affected to varying degrees by either hypoglycemia or uncontrolled diabetes mellitus.

Topics: Animals; Biological Transport; Blood Glucose; Blood-Brain Barrier; Brain; Diabetes Mellitus; Glucose; Glycogen; Humans; Insulin

This review introduces physiologists and clinical investigators to an ever-widening array of nuclear magnetic resonance applications. In particular, it highlights a multiple tracer technique that provides a comprehensive picture of metabolic processes within human liver.. Magnetic resonance spectroscopy is an important technique for studying metabolism in the brain, liver, heart and skeletal muscle. One fundamental advantage is that the studies are inherently noninvasive, so time-dependent information can be obtained. For example, 31P nuclear magnetic resonance investigations indicate that greater maximal oxygen uptake and oxidative capacity in trained athletes can be partially attributed to adaptations enhancing the rates at which phosphocreatine and inorganic phosphate recover during stress. In-vivo measurements of lipids and glycogen by 1H and 13C spectroscopy demonstrate that accumulation of intracellular lipids and impaired rates of glycogen synthesis contribute to insulin resistance and type 2 diabetes mellitus. Similar techniques can be used to analyze blood and urine samples obtained during administration of 2H or 13C tracers to yield information that cannot be easily obtained by mass spectrometry. Additional information available from nuclear magnetic resonance yields a comprehensive picture of liver metabolic pathways from a single clinical study.. A variety of magnetic resonance spectroscopy protocols have been validated and exploited for clinical studies, but relatively few investigators are comfortable with technical aspects of these protocols and utilize them for clinical research. Increased interaction between spectroscopists and other investigators is needed if the potential of nuclear magnetic resonance for studying in-vivo metabolism is to be fully realized.

Topics: Carbon Isotopes; Diabetes Mellitus; Energy Metabolism; Glycogen; Humans; Liver; Magnetic Resonance Spectroscopy; Muscles; Phosphorus Isotopes; Protons

The brain contains a significant amount of glycogen that is an order of magnitude smaller than that in muscle, but several-fold higher than the cerebral glucose content. Although the precise role of brain glycogen to date is unknown, it seems affected by focal activation, neurotransmitters, and overall electrical activity and hormones. Based on its relatively low concentration, the role of brain glycogen as a significant energy store has been discounted. This work reviews recent experimental evidence that brain glycogen is an important reserve of glucose equivalents: (1) glial glycogen can provide the majority of the glucose supply deficit during hypoglycemia for more than 100 min, consistent with the proposal that glial lactate is a fuel for neurons; (2) glycogen concentrations may be as high as 10 micromol/g, substantially higher than was thought previously; (3) glucose cycling in and out of glycogen amounts to approximately 1% of the cerebral metabolic rate of glucose (CMRglc) in human and rat brain, amounting to an effective stability of glycogen in the resting awake brain during euglycemia and hyperglycemia, (4) brain glycogen metabolism/concentrations are insulin/glucose sensitive; and (5) after a single episode of hypoglycemia, brain glycogen levels rebound to levels that exceed the pre-hypoglycemic concentrations (supercompensation). This experimental evidence supports the proposal that brain glycogen may be involved in the development of diabetes complications, specifically impaired glucose sensing (hypoglycemia unawareness) observed clinically in some diabetes patients under insulin treatment. It is proposed further that brain glycogen becomes important in any metabolic state where supply transiently cannot meet demand, such conditions that could occur during prolonged focal activation, sleep deprivation, seizures, and mild hypoxia.

Topics: Animals; Brain; Cell Communication; Diabetes Complications; Diabetes Mellitus; Energy Metabolism; Glycogen; Humans; Hypoglycemia; Neuroglia; Neurons

Skeletal muscle is the primary site of whole-body glucose disposal and is vital in determining the overall insulin sensitivity and carbohydrate management. Insulin and physical exercise are important stimuli for muscle glucose transport and glycogen metabolism. While it is known that both insulin and contraction stimulate muscle glucose uptake and glycogen metabolism, the post-receptor mechanisms are not completely understood. Local metabolic factors, such as adenosine, have been suggested to play a role in insulin and contraction regulation of carbohydrate metabolism in skeletal muscle. While adenosine has clearly been shown to potentiate insulin-stimulated glucose transport in adipocytes and heart muscle, its role in carbohydrate metabolism in skeletal muscle is less clear, with numerous diverging findings published to date. This review article summarizes findings on the putative roles of adenosine in insulin and exercise-mediated regulation of carbohydrate metabolism and the signalling pathways proposed to be central to these metabolic stimuli in skeletal muscle.

Topics: Adenosine; Animals; Diabetes Mellitus; Exercise; Glucose; Glucose Transporter Type 4; Glycogen; GTP-Binding Proteins; Homeostasis; Humans; Monosaccharide Transport Proteins; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Obesity; Physical Conditioning, Animal; Receptors, Purinergic P1; Signal Transduction; Xanthines

Topics: Animals; Blood Glucose; Diabetes Mellitus; Fasting; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucokinase; Glucose; Glucose Transporter Type 2; Glycogen; Humans; Insulin; Insulin Secretion; Intestinal Absorption; Liver; Monosaccharide Transport Proteins; Peptide Fragments; Protein Precursors

Topics: Adipose Tissue; Adrenocortical Hyperfunction; Diabetes Mellitus; Glucocorticoids; Gluconeogenesis; Glycogen; Glycolysis; Humans; Insulin Resistance; Liver; Muscles

Simultaneous synthesis and breakdown of glycogen is called glycogen cycling. The extent of hyperglycemia and decreased glycogen stores in diabetes mellitus may relate in part to the extent cycling occurs. Four methods have been introduced to estimate its extent in liver in humans. 1) In the fasted state, the rate of net hepatic glycogenolysis, i.e., glycogen breakdown minus synthesis, is estimated using NMR, and the rate of glycogenolysis is estimated from deuterium labeling of blood glucose on (2)H(2)O ingestion. 2) The rate of glycogen synthesis is estimated from the rate of labeling of carbon 1 of glycogen on [1-(13)C]glucose infusion, monitored by NMR, and the rate of breakdown from the rate of disappearance of that labeling on unlabeled glucose infusion. 3) The rate of synthesis from glucose-1-P, formed by glycogenolysis, is measured by the decrease in the (3)H/(14)C ratio in acetaminophen glucuronide on acetaminophen and [2-(3)H,6-(14)C]galactose administration. 4) The rate of synthesis is estimated from the dilution of label from labeled galactose in its conversion to the acetaminophen glucuronide, and the rate of glycogenolysis is estimated from the amount of label in blood glucose. In the first method, the fate of glucose-6-P is assumed to be only to glycogen and glucose. In the second, only glucose-6-P molecules formed by breakdown that are not cycled back to glycogen are measured. In the third, (3)H is assumed to be removed completely during cycling, and only the molecules cycled back to glycogen are measured. In the fourth, galactose conversion to glucose is assumed to be via glycogen. Quantitations in all four methods depend on assuming the order in which the molecules deposited in glycogen are released.

Topics: Animals; Carbon Isotopes; Deuterium; Diabetes Mellitus; Fasting; Galactose; Glucose; Glucuronides; Glycogen; Humans; Liver; Magnetic Resonance Spectroscopy; Tritium

The liver plays an important role in glucose homeostasis. In the postabsorptive state, plasma glucose is regulated by both hepatic glucose output(HGO) and peripheral glucose utilization(PGU). Insulin and glucagon regulate both HGO and PGU. Increased HGO and decreased PGU, suggesting insulin resistances bring increased fasting blood glucose. While glucose homeostasis after glucose ingestion is regulated by several factors. The regulation of hepatic glucose uptake(HGU) occurs by way of the hormonal milieu(insulin and glucagon), the glucose level, and the rote of glucose delivery. The presence of coordinated changes in insulin, glucagon and the glucose level in combination with the portal signal ensures adequate HGU in response to liver. Hepatic insulin resistance(increased HGO and decreased HGU) and peripheral insulin resistance(decreased PGU) are the characters of glucose intolerance.

Topics: Animals; Diabetes Mellitus; Glucagon; Glucose; Glycogen; Humans; Insulin; Insulin Resistance; Liver

Topics: Diabetes Mellitus; Fatty Acids; Glucose; Glycogen; Humans; Insulin; Insulin Resistance; Models, Biological; Muscles

Glucose is stored in mammalian tissues in the form of glycogen. Glycogen levels are markedly reduced in liver or muscle cells of patients with insulin-resistant or insulin-deficient forms of diabetes, suggesting that impaired glycogen synthesis may contribute to development of hyperglycemia. Recently, interest in this area has been further stimulated by new insights into the spatial organization of metabolic enzymes within cells and the importance of such organization in regulation of glycogen metabolism. It is now clear that a four-member family of glycogen targeting subunits of protein phosphatase-1 (PP1) plays a major role in coordinating these events. These proteins target PP1 to the glycogen particle and also bind differentially to glycogen synthase, glycogen phosphorylase, and phosphorylase kinase, thereby serving as molecular scaffolds. Moreover, the various glycogen-targeting subunits have distinct tissue expression patterns and can influence regulation of glycogen metabolism in response to glycogenic and glycogenolytic signals. The purpose of this article is to summarize new insights into the structure, function, regulation, and metabolic effects of the glycogen-targeting subunits of PP1 and to evaluate the possibility that these molecules could serve as therapeutic targets for lowering of blood glucose in diabetes.

Topics: Animals; Diabetes Mellitus; Glucose; Glycogen; Humans; Phosphoprotein Phosphatases; Protein Isoforms; Protein Phosphatase 1; Structure-Activity Relationship

Glutamine is the most abundant amino acid in the human body and is involved in more metabolic processes than any other amino acid. Until recently, the understanding of many aspects of glutamine metabolism was based on animal and in vitro data. However, recent studies using isotopic and balance techniques have greatly advanced the understanding of glutamine metabolism in humans and its role in glucose metabolism in the kidney and other tissues. There is now evidence that in postabsorptive humans, glutamine is an important glucose precursor and makes a significant contribution to the addition of new carbon to the glucose carbon pool. The importance of alanine for gluconeogenesis, viewed in terms of the addition of new carbons, is less than previously assumed. It appears that glutamine is predominantly a renal gluconeogenic substrate, whereas alanine gluconeogenesis is essentially confined to the liver. As shown recently, renal gluconeogenesis contributes 20 to 25% to whole-body glucose production. Moreover, glutamine has been shown not only to stimulate net muscle glycogen storage but also to stimulate gluconeogenesis in normal humans. Finally, in humans with type II diabetes, conversion of glutamine to glucose is increased (more so than that of alanine). The available evidence on the hormonal regulation of glutamine gluconeogenesis in kidney and liver and its alterations under pathological conditions are discussed.

Topics: Alanine; Animals; Carbohydrate Metabolism; Diabetes Mellitus; Gluconeogenesis; Glutamine; Glycogen; Humans; In Vitro Techniques; Kidney; Liver; Muscles

Diabetes affects 3% of the European population and 140 million people worldwide, and is largely a disease of insulin resistance in which the tissues fail to respond to this hormone. This emphasizes the importance of understanding how insulin signals to the cell's interior. We have recently dissected a protein kinase cascade that is triggered by the formation of the insulin 'second messenger' phosphatidylinositide (3,4,5) trisphosphate (PtdIns (3,4,5)P3) and which appears to mediate many of the metabolic actions of this hormone. The first enzyme in the cascade is termed 3-phosphoinositide-dependent protein kinase-1 (PDK1), because it only activates protein kinase B (PKB), the next enzyme in the pathway, in the presence of PtdIns (3,4,5)P3. PKB then inactivates glycogen synthase kinase-3 (GSK3). PDK1, PKB and GSK3 regulate many physiological events by phosphorylating a variety of intracellular proteins. In addition, PKB plays an important role in mediating protection against apoptosis by survival factors, such as insulin-like growth factor-1.

Topics: 3-Phosphoinositide-Dependent Protein Kinases; Amino Acid Sequence; Apoptosis; Calcium-Calmodulin-Dependent Protein Kinases; Diabetes Mellitus; Enzyme Inhibitors; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Humans; Insulin; Molecular Sequence Data; Phosphatidylinositol Phosphates; Phosphorylation; Protein Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptor, Insulin; Signal Transduction

Topics: Amino Acids; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fructose; Gluconeogenesis; Glycerol; Glycogen; Homeostasis; Humans; Insulin; Lactates; Obesity

Topics: Diabetes Mellitus; Glucokinase; Glucose; Glucose-6-Phosphate; Glycogen; Glycolysis; Hexokinase; Humans; Insulin; Insulin Secretion; Liver; Mutation

Topics: Biogenic Amines; Catecholamines; Diabetes Mellitus; Gluconeogenesis; Glycogen; Glycolysis; Humans

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Glucose; Glycogen; Humans

Topics: Animals; Chromans; Diabetes Mellitus; Disease Models, Animal; Glycogen; Glycolysis; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Liver; Thiazoles; Thiazolidinediones; Troglitazone

Topics: Animals; Diabetes Mellitus; Disease Models, Animal; Glycogen; Glycolysis; Hypoglycemic Agents; Insulin Resistance; Liver; Pioglitazone; Thiazoles; Thiazolidinediones

Topics: Animals; Biomarkers; Cell Membrane Permeability; Cytoplasm; Deoxyglucose; Diabetes Mellitus; Glycogen; Humans; Kidney; Lyases

Natural-abundance 13C nuclear magnetic resonance (NMR) spectroscopy is a noninvasive technique that enables in vivo assessments of muscle and/or liver glycogen concentrations. When directly compared with the traditional needle biopsy technique, NMR was found to be more precise. Over the last several years, we have developed and used 13C-NMR to obtain information about human glycogen metabolism both under conditions of altered blood glucose and/or insulin and with exercise. Because NMR is noninvasive, we have been able to obtain more data points over a specified time course, thereby dramatically improving the time resolution. This improved time resolution has enabled us to document subtleties of the resynthesis of muscle glycogen after severe exercise that have not been observed previously. An added advantage of NMR is that we are able to obtain information simultaneously about other nuclei, such as 31P. With interleaved 13C- and 31P-NMR techniques, we have been able to follow simultaneous changes in muscle glucose-6-phosphate and muscle glycogen. In this article, we review some of the work that has been reported by our laboratory and discuss the relevance of our findings for the management of diabetes.

Topics: Animals; Diabetes Mellitus; Glucosephosphates; Glycogen; Magnetic Resonance Spectroscopy; Muscles; Physical Exertion; Rabbits; Rats

Abnormal liver tests, right upper quadrant pain and hepatomegaly occurring in an obese or in a diabetic patient may point to the presence of fat or of glycogen accumulation in the liver parenchymal cells. Marked hepatomegaly due to cytoplasmic glycogen deposition is mainly found in poorly controlled insulin-dependent diabetic patients. If accompanied by cushingoid features, growth retardation and by delayed puberty, a diagnosis of Mauriac syndrome can be made. Hyperglycaemia, insulin administration and increased concentrations of the counterregulatory hormone cortisol may all play a role in the glycogen deposition by their concerted actions on the glycogen phosphorylase and synthase enzymes, promoting the accumulation of glycogen. Hypercortisolism may be responsible for growth retardation and delayed puberty in Mauriac patients. Regression of hepatomegaly and of the associated clinical characteristics may be obtained by a better metabolic control due to the administration of long-acting insulin and the change from single to twice daily injections. Fatty liver is rare in insulin-dependent diabetic patients and is indicative of a poor diabetic control. This process is quickly reversible by adequate insulin treatment. Steatosis is frequently found in maturity-onset diabetics and in obese patients. The pathogenetic mechanisms leading to the accumulation of triglycerides and of fatty acids in the hepatocytes can easily be understood from the normal cycling of fatty acids between the adiopose tissue and the liver. Histologic features of nonalcoholic steatohepatitis can also be found in obese and in diabetic patients. Steatohepatitis may rarely evolve into cirrhosis. In general, there is no correlation between the degree of the biochemical alterations and the severity of the histological findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Diabetes Complications; Diabetes Mellitus; Fatty Acids; Fatty Liver; Glycogen; Humans; Liver; Obesity; Triglycerides

Orally taken alpha-glucosidase inhibitors are used for the management of diabetes mellitus. These drugs can prevent the postprandial rise of the blood glucose level by inhibiting the enzymatic digestion of carbohydrates in the intestinal lumen. Non-absorbable inhibitors such as acarbose are expected to function exclusively in the intestine, but absorbable inhibitors such as miglitol may exert an inhibitory effect on non-intestinal alpha-glucosidases present in the various cell types of the body. The potential side-effects of absorbable inhibitors are evaluated in this literature review. It is concluded that there is little risk of inducing unwanted side-effects when miglitol is taken in an oral dose of approximately 1 mg kg-1 body weight. The use of absorbable inhibitors is, however, not advised in case of kidney dysfunction.

Topics: 1-Deoxynojirimycin; Acarbose; Administration, Oral; Animals; Blood Glucose; Carbohydrate Sequence; Contraindications; Diabetes Mellitus; Diabetic Nephropathies; Glucosamine; Glycogen; Glycogen Storage Disease; Glycoproteins; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Imino Pyranoses; Molecular Sequence Data; Sucrase-Isomaltase Complex; Trisaccharides

A metabolic hypothesis is presented for insulin resistance in obesity, in the presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is based on physiological mechanisms including a series of negative feed-back mechanisms, with the inhibition of the function of the glycogen cycle in skeletal muscle as a consequence of decreased glucose utilization resulting from increased lipid oxidation in the obese. It considers the inhibition of glycogen synthase activity together with inhibition of glucose storage and impaired glucose tolerance. The prolonged duration of increased lipid oxidation, considered as the initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with others based on the inhibition of insulin receptor kinase and of glucose transporter activities.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose; Glycogen; Homeostasis; Humans; Insulin Resistance; Models, Biological; Muscles; Obesity

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipid Metabolism; Obesity; Oxidation-Reduction; Risk Factors

In summary, the appropriate balance of glucagon and insulin at the liver and the catecholamines and insulin in the periphery provide the most optimal balance of substrate fluxes to the working muscle. When the hormonal balance is perturbed such as is seen in diabetes or with glucagon suppression, or when the effect of a hormone is impaired such as with beta blockade, optimal substrate balance is lost. The effects of these hormones can be overridden by metabolic factors in muscle, as evidenced by the uncoupling of the normal catecholamine antagonism of glucose uptake from the actual glucose uptake observed during exercise under conditions of tissue hypoxia.

Topics: Animals; Blood Glucose; Catecholamines; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dogs; Glucagon; Glucose; Glycogen; Humans; Insulin; Liver; Muscles; Physical Exertion; Somatostatin

Altered glucose homeostasis in the neonate often results from antecedent events during fetal life. This article describes the normal and altered development of glucoregulatory capabilities during perinatal life and relates it to problems of hypo- and hyperglycemia in the neonate.

Topics: Diabetes Mellitus; Embryonic and Fetal Development; Female; Fetus; Gluconeogenesis; Glucose; Glycogen; Homeostasis; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Infant, Premature; Mass Screening; Maternal-Fetal Exchange; Pregnancy; Pregnancy in Diabetics; Risk

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Energy Metabolism; Exercise Therapy; Fatty Acids, Nonesterified; Food; Glucose; Glucose Tolerance Test; Glycogen; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Liver; Muscles; Physical Exertion; Quality of Life

Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.

Topics: Adrenergic beta-Agonists; Animals; Cyclic AMP; Diabetes Mellitus; Estrogens; Female; Fetus; Glucocorticoids; Glycogen; Humans; Lipids; Lung; Parasympathomimetics; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylglycerols; Pregnancy; Prolactin; Prostaglandins; Pulmonary Surfactants; Subcellular Fractions; Thyrotropin-Releasing Hormone

Topics: Blood Glucose; Cyclic AMP; Diabetes Mellitus; Epinephrine; Glucagon; Glucocorticoids; Glucose; Glycogen; Growth Substances; Homeostasis; Hormones; Humans; Insulin; Intestinal Absorption; Lipolysis; Liver; Receptors, Adrenergic; Somatostatin; Thyroid Hormones

Topics: Adipose Tissue; Autoantibodies; Blood Glucose; Cell Membrane; Diabetes Mellitus; Diet, Reducing; Fatty Acids; Glucose; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Obesity; Receptor, Insulin; Triglycerides

Topics: Adipose Tissue; Animals; Diabetes Mellitus; Enzyme Activation; Fasting; Food; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Synthase; Hormones; Kinetics; Nutritional Physiological Phenomena; Rats

On the basis of analysis of the literature and the author's data a hypothesis of transformation of lipids into glycogen in animal and human cells by means of microbodies and lysosomes as one of the universal adaptative reactions of the host is substantiated. In the opinion of the author, both microbodies and lysosomes may take part both in the process of oxidation of intracellular lipids up to intermediate metabolism products and in the process of glycogen synthesis from these products. As a result of enhanced oxidation and transformation of lipids into glycogen the energy of the cell improves and the possibility of development of fatty dystrophy decreases. The hypothesis is based on the structural association of microbodies, lysosomes, fatty and glycogen inclusions observed by the author in cells of various organs in different pathological processes, as well as on certain biochemical data.

Topics: Adrenal Glands; Animals; Biotransformation; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dogs; Fasting; Gluconeogenesis; Glycogen; Histocytochemistry; Humans; Lipid Metabolism; Liver Glycogen; Lysosomes; Microbodies; Myocardium; Rats; Skin

Topics: Adipose Tissue; Alanine; Animals; Biological Transport; Brain; Diabetes Mellitus; Dogs; Fatty Acids, Nonesterified; Fetus; Glucose; Glycogen; Goats; Humans; Ketone Bodies; Lipid Metabolism; Liver; Lung; Muscles; Myocardium; Rats; Starvation; Tissue Distribution

In a survey, the pharmacological and clinical documentation of metformin is presented and discussed, and the present state of knowledge relating to metformin-associated lactic acidosis is reviewed. The use of metformin in the treatment of diabetes is based on clinical experience over twenty years. It has been well documented that metformin is effective in maturity-onset diabetes both as monotherapy and in combination with a sulphonylurea. An advantage of metformin treatment is the tendency to weight reduction and the absence of significant hypoglycaemia; blood glucose levels are reduced only to normal. The disadvantages are the gastro-intestinal side effects and the potential risk of vitamin B 12 and folic acid deficiency during long-term use. Metformin-associated lactic acidosis is a very rare complication, which has mainly occured in patients with serious renal insufficiency or other contra-indications to the use of metformin. The association between phenformin and lactic acidosis has led to withdrawal of this biguanide in several countries. Metformin differs from phenformin in certain important respects, and the normal use of metformin does not involve the risk of side effects disproportionate to the intended effect. Further experimental studies are required to substantiate pharmacokinetics and metabolic effects of metformin in man.

Topics: Animals; Body Weight; Diabetes Mellitus; Gluconeogenesis; Glucose; Glycogen; Humans; Insulin; Insulin Secretion; Intestinal Absorption; Islets of Langerhans; Lipid Metabolism; Metformin; Muscles

Topics: Animals; Blood Glucose; Cyclic AMP; Diabetes Mellitus; Fasting; Glucocorticoids; Gluconeogenesis; Glucose; Glycogen; Glycogen Synthase; Homeostasis; Insulin; Kinetics; Liver; Phosphoric Monoester Hydrolases; Phosphorylase Kinase; Phosphorylase Phosphatase; Phosphorylases; Protein Kinases; Splanchnic Nerves

Topics: Adipose Tissue; Aging; Animals; Antibody Formation; Cattle; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fatty Acids; Glucose; Glycogen; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Ketone Bodies; Lipid Metabolism; Liver; Muscles; Rabbits; Triglycerides

Topics: Adrenal Cortex Hormones; Animals; Carbohydrate Metabolism; Diabetes Mellitus; Enzyme Induction; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose; Glycogen; Humans; Hydrocortisone; Lipid Metabolism; Lipid Mobilization; Lipids; Liver; Muscle Proteins; Muscles; Phosphoenolpyruvate Carboxykinase (GTP); Phosphoric Monoester Hydrolases; Proteins; Rats; Transaminases

Topics: Blood Glucose; Blood Proteins; Diabetes Mellitus; Fructosephosphates; Glucose; Glucosephosphates; Glycogen; Glycogen Synthase; Glycolysis; Humans; Hydrogen-Ion Concentration; Insulin; Kinetics; Lactates; Lipids; Neutrophils; Oxygen Consumption; Pentoses; Phagocytosis; Phosphofructokinase-1

Topics: Adipose Tissue; Animals; Blood Glucose; Catecholamines; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glucose; Glycogen; Lipid Metabolism; Liver; Liver Glycogen; Metabolism; Muscles; Myocardium; Rabbits; Rats; Receptors, Adrenergic

Topics: Amino Acids; Animals; Blood Glucose; Cross Reactions; Diabetes Mellitus; Glucagon; Gluconeogenesis; Glycogen; Humans; Insulin; Insulin Secretion; Intestinal Mucosa; Lipid Mobilization; Liver; Stress, Physiological

Topics: Amino Acids; Biological Transport; Carbohydrate Metabolism; Cell Division; Cells, Cultured; Clone Cells; Collagen; Culture Media; Diabetes Mellitus; Diploidy; DNA; Fibroblasts; Genetic Variation; Genetics, Medical; Glucosephosphate Dehydrogenase; Glycogen; Glycosaminoglycans; Humans; Insulin; Lesch-Nyhan Syndrome; Lipid Metabolism; Molecular Biology; Mutation; Orotic Acid; RNA

Topics: Amino Acids; Cyclic AMP; Diabetes Mellitus; Digestive System; Fatty Acids, Nonesterified; Glucagon; Gluconeogenesis; Glucose; Glycogen; Humans; Hyperglycemia; Insulin; Insulin Secretion; Liver Glycogen; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms

Topics: Abdomen; Animals; Biopsy; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Epinephrine; Glucagon; Gluconeogenesis; Glucose; Glycogen; Humans; Insulin; Liver; Muscle Contraction; Muscles; Nucleotides; Physical Exertion; Proteins; Rats; Starvation; Wounds and Injuries

Topics: Acid-Base Equilibrium; Adipose Tissue; Amino Acids; Blood Glucose; Cell Membrane Permeability; Diabetes Mellitus; Dietary Carbohydrates; Dietary Proteins; Fasting; Feedback; Gluconeogenesis; Glucose; Glycogen; Homeostasis; Humans; Insulin; Ketone Bodies; Lipid Metabolism; Liver; Liver Glycogen; Metabolism; Muscle Proteins; Muscles; Nitrogen; Obesity; Pancreas; Wounds and Injuries

Topics: Adipose Tissue; Blood Glucose; Cell Membrane Permeability; Cytoplasm; Diabetes Mellitus; Diabetic Coma; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Glycosuria, Renal; Humans; Hyperglycemia; Insulin; Lipid Metabolism; Liver; Mitochondria; Muscles; Pancreas; Pancreatectomy; Proteins; Time Factors

Topics: Acetone; Acetylcholine; Adenosine Triphosphate; Adult; Aged; Blood Glucose; Capillary Permeability; Copper; Diabetes Mellitus; Glutathione; Glycogen; Histamine; Humans; Iron; Middle Aged

Topics: Acid Phosphatase; Adult; Animals; Citric Acid Cycle; Diabetes Mellitus; Erythroblastosis, Fetal; Female; Glycogen; Glycolysis; Histocytochemistry; Humans; Hyperglycemia; Infant, Newborn; Insulin; Islets of Langerhans; Lysosomes; Mice; Obesity; Pentosephosphates; Pregnancy; Transaminases

Topics: Acidosis; Adipose Tissue; Animals; Animals, Laboratory; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Feeding Behavior; Glycogen; Guinea Pigs; Haplorhini; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Ketone Bodies; Mice; Muscles; Obesity; Pancreas; Prediabetic State; Rats

Topics: Adipose Tissue; Animals; Brain; Carbohydrate Metabolism; Diabetes Mellitus; Epinephrine; Erythrocytes; Glucagon; Glucocorticoids; Glucose; Glycogen; Glycolysis; Growth Hormone; Homeostasis; Humans; Insulin; Kidney; Muscles; Skin; Triglycerides

Topics: Adipose Tissue; Animals; Biological Transport; Congenital Abnormalities; Diabetes Mellitus; Dialysis; Diaphragm; Fatty Acids, Nonesterified; Female; Glucose; Glucose Tolerance Test; Glycogen; Growth Hormone; Humans; Hypoglycemia; Insulin; Insulin Antagonists; Insulin Antibodies; Muscles; Obesity; Peptides; Prediabetic State; Pregnancy; Pregnancy in Diabetics; Serum Albumin

Topics: Adenine Nucleotides; Animals; Carbohydrate Metabolism; Cyclic AMP; Diabetes Mellitus; Epinephrine; Glucagon; Gluconeogenesis; Glycogen; Humans; Insulin; Insulin Secretion; Lipid Metabolism; Liver; Muscles; Prediabetic State

Topics: Animals; Brain Chemistry; Diabetes Mellitus; Diuretics; Glycogen; Hepatolenticular Degeneration; Humans; Hypercholesterolemia; Hyperlipidemias; Liver; Liver Diseases; Poisoning; Skin Diseases; Thioctic Acid

Topics: Diabetes Mellitus; Fatty Liver; Glycogen; Hemochromatosis; Hepatitis; Hepatitis A; Humans; Insulin; Liver; Liver Cirrhosis

Topics: Alanine Transaminase; Aspartate Aminotransferases; Clinical Enzyme Tests; Diabetes Mellitus; Fatty Liver; Glycogen; Glycogen Storage Disease; Hepatitis; Hepatitis A; Humans; Jaundice; Liver Cirrhosis; Liver Diseases; Liver Glycogen; Splenomegaly

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Glucose; Glycogen; Humans; Insulin; Lactates; Leukocytes; Metabolism; Pyruvates

Explore whether Glycogen synthesis kinase-3β (GSK3β) involved in the analgesic effect of liraglutide on diabetic neuropathic pain (DNP).. DNP was induced by streptozocin (STZ) in WT and GSK3β(S9A) mice, which carried a constitutively active form of GSK3β. DNP mice were intracerebroventricularly injected with liraglutide 5 weeks after STZ injection. The behavior of neuropathic pain was evaluated 2 h after drugs administration. The microglial activation and the expression of NOD-like receptor protein 3 (NLRP3) in microglia in cortex were evaluated. The role of GSK3β in the inhibitory effect of liraglutide on the NLRP3 inflammasome was explored in BV2 microglia.. Intracerebroventricular administration of liraglutide significantly relieved neuropathic pain and inhibited the activation of cortical microglia in WT mice with DNP. But the effect of liraglutide disappeared in GSK3β(S9A) mice. In BV2 microglia, GSK3β inhibitor significantly suppressed NLRP3 inflammasome activation. And activating GSK3β through GSK3β(S9A) lentivirus significantly blocked the inhibitory effect of liraglutide on NLRP3 inflammasome in BV2 microglia. Intracerebroventricular administration of liraglutide significantly inhibited the expression of NLRP3 in cortex microglia of DNP group in WT mice but failed in GSK3β(S9A) mice.. GSK3β involves in the analgesic effect of liraglutide on DNP through NLRP3 inflammasome in microglia.

Topics: Analgesics; Animals; Diabetes Mellitus; Diabetic Neuropathies; Glycogen; Glycogen Synthase Kinase 3 beta; Inflammasomes; Liraglutide; Mice; Neuralgia; NLR Family, Pyrin Domain-Containing 3 Protein

Diabetes associated with post-menopause is related to a worse condition of kidney disease. Taking into consideration that this disorder may be regulated by estrogenic mediators, we evaluated the renal protective effect of isoflavone. We investigated the role of the PPARγ in the pathogenesis of the disease. For this study, we used diabetic female rats in a postmenopausal model through ovariectomy. The animals were treated with isoflavone or 17β-estradiol. A dosage was administered to bring on blood glycemia, and through immunohistochemistry, we evaluated the immunoreactivity of PPARγ in the endometrium and renal tissue. We analyzed the immunoreactivity of renal injury molecule KIM-1 and the collagen and glycogen densities in the kidney. Through bioinformatics analysis, we observed

Topics: Animals; Diabetes Mellitus; Estradiol; Female; Glycogen; Humans; Isoflavones; Ovariectomy; PPAR gamma; Rats

Diabetes is a chronic metabolic disease, whereas α-glucosidases are key enzymes involved in the metabolism of starch and glycogen. There is a long history of the use of mulberry leaf (the leaf of

Topics: Acarbose; alpha-Glucosidases; Benzofurans; Diabetes Mellitus; Glycogen; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Morus; Plant Leaves; Starch

Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca. Animals and humans move by contracting the skeletal muscles attached to their bones. These muscles take up a type of sugar called glucose from food and use it to fuel contractions or store it for later in the form of glycogen. If muscles fail to use glucose it can lead to excessive sugar levels in the blood and a condition called diabetes. Within muscle cells are stores of calcium that signal the muscle to contract. Changes in calcium levels enhance the uptake of glucose that fuel these contractions. However, variations in calcium have also been linked to diabetes, and it remained unclear when and how these ‘signals’ become harmful. People with a condition called malignant hyperthermia susceptibility (MHS for short) have genetic mutations that allow calcium to leak out from these stores. This condition may result in excessive contractions causing the muscle to over-heat, become rigid and break down, which can lead to death if left untreated. A clinical study in 2019 found that out of hundreds of patients who had MHS, nearly half had high blood sugar and were likely to develop diabetes. Now, Tammineni et al. – including some of the researchers involved in the 2019 study – have set out to find why calcium leaks lead to elevated blood sugar levels. The experiments showed that enzymes that help convert glycogen to glucose are more active in patients with MHS, and found in different locations inside muscle cells. Whereas the enzymes that change glucose into glycogen are less active. This slows down the conversion of glucose into glycogen for storage and speeds up the breakdown of glycogen into glucose. Patients with MHS also had fewer molecules that transport glucose into muscle cells and stored less glycogen. These changes imply that less glucose is being removed from the blood. Next, Tammineni et al. used a microscopy technique that is able to distinguish finely separated objects with a precision not reached before in living muscle. This revealed that when the activity of the enzyme that breaks down glycogen increased, it moved next to the calcium store. This effect was also observed in the muscle cells of MHS patients that leaked calcium from their stores. Taken together, these observations may explain why patients with MHS have high levels of sugar in their blood. These findings suggest that MHS may start decades before developing diabetes and blood sugar levels in these patients should be regularly monitored. Future studies should investigate whether drug

Topics: Adult; Aged; Animals; Blood Glucose; Calcium; Diabetes Mellitus; Glucose; Glucose Transporter Type 4; Glycogen; Glycogen Phosphorylase, Muscle Form; Humans; Hyperglycemia; Malignant Hyperthermia; Mice; Middle Aged; Muscle, Skeletal; Phosphorylase Kinase; Phosphorylation

SDM and T2DM rat models were established. During this time, PET/CT imaging was used to measure the %ID/g value of skeletal muscle and liver to evaluate glucose uptake. The pancreatic, skeletal muscle and liver were analyzed by immunohistochemistry.. SDM rats showed increased fasting blood glucose and insulin levels, hyperplasia of islet α and β cells, increased FDG uptake in skeletal muscle accompanied by an up-regulation of PI3Kp85α, IRS-1, and GLUT4, no significant changes in liver uptake, and that glycogen storage in the liver and skeletal muscle increased. T2DM rats showed atrophy of pancreatic islet β cells and decreased insulin levels, significantly reduced FDG uptake and glycogen storage in skeletal muscle and liver.. The pathogenesis of SDM is different from that of T2DM. The increased glucose metabolism of skeletal muscle may be related to the increased compensatory secretion of insulin. Glucocorticoids promote the proliferation of islet α cells and cause an increase in gluconeogenesis in the liver, which may cause increased blood glucose.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Fluorodeoxyglucose F18; Glucocorticoids; Glucose Transporter Type 4; Glycogen; Humans; Insulin; Insulin Receptor Substrate Proteins; Liver; Male; Muscle, Skeletal; Positron Emission Tomography Computed Tomography; Rats; Rats, Wistar

Black truffle mushroom, Tuber melanosporum, is effective in treating various symptoms associated with diabetes mellitus such as hyperglycemia, oxidative stress, and hyperlipidemia and is used as traditional medicine. The aim of our study is to elucidate the antidiabetic potential of T. melanosporum. Male albino Wistar rats were administered a single dose of STZ (40 mg/kg b.w.) to induce mild diabetes mellitus (DM). After the confirmation of hyperglycemia, rats were treated with three different doses of truffle extract (TE) (200, 400, and 600 mg/kg b.w.) for the duration of 45 days. The various tissues were collected at the end of the study. The levels of glucose, oral glucose tolerance test, insulin, hexokinase, glucose 6 phosphatase, and fructose-1,6-bisphosphatase, and regulation of insulin signaling genes were quantified. The results showed that STZ- induced rats have a higher blood glucose level and a lower insulin level compared with the control groups and TE treated groups. Results also reveal that STZ suppressed the expressions of insulin signaling genes in diabetic rats and TE treatment resulted in a positive regulation of the insulin signaling pathway. The results of TE are similar to the results attained in glibenclamide (GB) group rats. Overall, the study provides scientific evidence for the medicinal properties of black truffle; future clinical studies can warrant a potential antidiabetic drug in the form of diet.

Topics: Animals; Ascomycota; Blood Glucose; Diabetes Mellitus; Glycogen; Hexokinase; Humans; Hypoglycemic Agents; Insulin; Liver; Male; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Signal Transduction; Streptozocin

Diabetes mellitus (DM) is one of the most common metabolic disorders worldwide and 425 million people were estimated to have diabetes by 2017. Oral manifestations reflect the metabolic control of diabetes. Exfoliative cytology using Papanicolaou (Pap) and periodic acid Schiff (PAS) stains is a practical technique to evaluate oral epithelial cytomorphologic changes in diabetes.. This study analyzes the cytomorphologic changes and the glycogen content in exfoliated oral epithelial cells among diabetic patients as compared to healthy controls using Pap and PAS stains to verify the utility of exfoliative cytology as adjunct to diagnosis, follow up or screening of diabetes.. Eighty-nine participants; 38 adult diabetic patients (case group) and 51 age-matching nondiabetics (control group) were enrolled in the study after fulfilling appropriate inclusion and exclusion criteria. Sampling and staining procedures were performed using routine protocols. Slides were observed by two pathologists and categorized as inflammatory, dyskaryotic and negative. Glycogen content was expressed as PAS negative or +, ++, and +++ positive.. The difference between the diabetics and the controls was statistically significant regarding inflammatory, dyskaryotic/nuclear changes and glycogen content and staining intensity. Other observed finding in diabetic patient smears included binucleation, polychromic, and/or vacuolated cytoplasm.. Cytomorphologic changes of oral epithelial cells reflect the complex pathological mechanisms by which DM affects cellular metabolism and function. Cytomorphologic patterns of Pap and PAS-stained oral exfoliative cytology smears can be helpful for diagnosis, follow up as well as for screening for diabetes in high prevalence communities.

Topics: Adult; Biomarkers; Case-Control Studies; Diabetes Mellitus; Female; Glycogen; Humans; Male; Middle Aged; Mouth Mucosa; Papanicolaou Test; Saudi Arabia

The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie diet consumption.

Topics: Adipose Tissue; alpha-Amylases; Animals; Apocynaceae; Carbohydrate Metabolism; Diabetes Mellitus; Diet, High-Fat; Disaccharidases; Disease Models, Animal; Dose-Response Relationship, Drug; Glycogen; Glycolysis; Hypoglycemic Agents; Insulin; Intestines; Liver; Male; Metformin; Phytotherapy; Plant Extracts; Plants, Medicinal; Psoas Muscles; Rats, Wistar

Phytoglycogen (from certain mutant plants) and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired.

Topics: Animals; Diabetes Mellitus; Glycogen; Humans; Hydrolysis; Liver Glycogen; Mice; Rats; Starch; Zea mays

Liver and muscle glycogen content is reduced in diabetic patients but there is no information on the effect of diabetes on the glycogen content in the retinal pigment epithelium (RPE). The main aim of the study was to compare the glycogen content in the RPE between diabetic and non-diabetic human donors. Glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, as well as their isoforms, were also assessed. For this purpose, 44 human postmortem eye cups were included (22 from 11 type 2 diabetic and 22 from 11 non-diabetic donors matched by age). Human RPE cells cultured in normoglycemic and hyperglycemic conditions were also analyzed. Glycogen content as well as the mRNA, protein content and enzyme activity of GS and GP were determined. In addition, GS and GP isoforms were characterized. In the RPE from diabetic donors, as well as in RPE cells grown in hyperglycemic conditions, the glycogen content was increased. The increase in glycogen content was associated with an increase in GS without changes in GP levels. In RPE form human donors, the muscle GS isoform but not the liver GS isoform was detected. Regarding GP, the muscle and brain isoform of GP but not the liver GP isoform were detected. We conclude that glycogen storage is increased in the RPE of diabetic patients, and it is associated with an increase in GS activity. Further studies aimed at determining the role of glycogen deposits in the pathogenesis of diabetic retinopathy are warranted.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus; Female; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Humans; Liver; Male; Middle Aged; Muscle, Skeletal; Retinal Pigment Epithelium; Tissue Donors

To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.. HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).. The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.. The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

Topics: Animals; Diabetes Mellitus; Drugs, Chinese Herbal; Enzyme Inhibitors; Glycogen; Glycogen Phosphorylase; Hep G2 Cells; Humans; Insulin; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Triterpenes

Small molecule glucokinase activators (GKAs) have been associated with potent antidiabetic efficacy and hepatic steatosis in rodents. This study reports the discovery of S 50131 and S 51434, two novel GKAs with an original scaffold and an atypical pharmacological profile.. Activity of the compounds was assessed in vitro by measuring activation of recombinant glucokinase, stimulation of glycogen synthesis in rat hepatocytes and increased insulin secretion from rat pancreatic islets of Langerhans. Efficacy and safety in vivo were evaluated after oral administration in db/db mice by measuring glycaemia, HbA1c and dyslipidaemia-associated events.. S 50131 and S 51434 activated GK and stimulated glycogen synthesis in hepatocytes and insulin secretion from pancreatic islets. Unexpectedly, while both compounds effectively lowered glycaemia after acute oral administration, they did not decrease HbA1c after a 4-week treatment in db/db mice. This lack of antidiabetic efficacy was associated with increased plasma free fatty acids (FFAs), contrasting with the effect of GKA50 and N00236460, two GKAs with sustained HbA1c lowering activity but neutral regarding plasma FFAs. S 50131, but not S 51434, also induced hepatic steatosis, as did GKA50 and N00236460. However, a shorter, 4-day treatment resulted in increased hepatic triglycerides without changing the plasma FFA levels, demonstrating dynamic alterations in the lipid profile over time.. In addition to confirming the occurrence of dyslipidaemia with GKAs, these findings provide new insights into understanding how such compounds may sustain or lose efficacy over time.

Topics: Animals; Blood Glucose; Caco-2 Cells; Cells, Cultured; Cholesterol; Diabetes Mellitus; Enzyme Activators; Fatty Acids, Nonesterified; Glucokinase; Glycated Hemoglobin; Glycogen; Hepatocytes; Humans; Hypoglycemic Agents; Insulin; Intestinal Absorption; Islets of Langerhans; Liver; Male; Mice; Nicotinic Acids; Polycyclic Compounds; Rats, Sprague-Dawley; Rats, Wistar; Treatment Outcome; Triglycerides

Topics: Diabetes Mellitus; Eccrine Glands; Glycogen; Humans; Skin Diseases

In Indian traditional system of medicine, Ficus religiosa (Family Moraceae) is prescribed for the treatment of diabetes mellitus. In the present study, the antidiabetic effect of aqueous extract of Ficus religiosa bark (FRAE) was investigated in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.. Oral administration of FRAE at the doses of 25, 50 and 100mg/kg was studied in normal, glucose-loaded and STZ-diabetic rats.. The three doses caused significant reduction in blood glucose levels in all the models. The effect was more pronounced in 50 and 100mg/kg than 25mg/kg. FRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle of STZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. FRAE also showed significant antilipidperoxidative effect in the pancreas of STZ-induced diabetic rats. The antidiabetic effect of Ficus religiosa was compared with glibenclamide, a well-known hypoglycemic drug.. The results indicate that aqueous extract of Ficus religiosa bark possesses significant antidiabetic activity.

Topics: Administration, Oral; Animals; Body Weight; Cholesterol; Diabetes Mellitus; Ficus; Glyburide; Glycogen; Hypoglycemic Agents; Insulin; Liver; Male; Pancreas; Rats; Rats, Wistar; Streptozocin; Triglycerides

The significance of clear cell change (clear reticulated cytoplasmic change) in the secretory portion of eccrine glands remains an enigma. It has been postulated to be a product of defective cellular glucose metabolism and potentially a predictor of diabetes. A series of 61 specimens from 38 patients were assessed to establish any demographic, seasonal, or metabolic associations. Sixty-one specimens from 38 patients with eccrine clear cell changes were identified prospectively by one of the authors (T.W.B.). Each specimen was stratified by site, age, sex, and season. For each patient, the general practitioner was contacted and diabetes status was ascertained. This was possible in 34 of 38 patients. Fifty routine consecutive cases from the archive in both summer and winter were studied for possible clear cell changes, looking for any seasonal variance. No clear association between the presence of eccrine clear cell change and any demographic or seasonal pattern was found. Specifically, there did not seem to be any significant association between diabetes and this histological finding. The prevalence of diabetes in cases with eccrine clear cell change was similar to the background population prevalence of diabetes in Australia (7.9% vs. 7.4%). The incidence of this finding is approximately 1 case in 189 specimens (0.5%) examined in this practice. Clear cell change within the secretory portion of eccrine glands seems to be an incidental finding, with no clear clinicopathological implication. In particular, there does not seem to be any association with diabetes.

Topics: Comorbidity; Diabetes Mellitus; Eccrine Glands; Female; Glycogen; Humans; Male; Periodic Acid-Schiff Reaction; Seasons; Skin Diseases; Western Australia

Protein hepatocyte nuclear factor 4alpha (HNF-4alpha) is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. HNF-4alpha and Foxo1 can physically interact with each other and represent an important signal transduction pathway that regulates the synthesis of glucose in the liver. Foxo1 and HNF-4alpha interact with their own binding sites in the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) promoters, and this binding is required for their effects on those promoters. However, the effect of physical activity on the HNF-4alpha/Foxo1 pathway is currently unknown. Here, we investigate the protein levels of HNF-4alpha and the HNF-4alpha/Foxo1 pathway in the liver of leptin-deficient (ob/ob) and diet-induced obese Swiss (DIO) mice after acute exercise. The ob/ob and DIO mice swam for four 30 min periods, with 5 min rest intervals for a total swimming time of 2h. Eight hours after the acute exercise protocol, the mice were submitted to an insulin tolerance test (ITT) and determination of biochemical and molecular parameters. Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions. These phenomena were accompanied by a reduction in the expression of gluconeogenesis genes, such as PEPCK and G6Pase. Importantly, the PI3K inhibitor LY292004 reversed the acute effect of exercise on fasting hyperglycaemia, confirming the involvement of the PI3K pathway. The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway. Since nuclear localization and the association of these proteins is involved in the activation of PEPCK and G6Pase, we believe that the regulation of Foxo1 and HNF-4alpha activities are important mechanisms involved in exercise-induced improvement of glucose homeostasis in insulin resistant states.

Topics: Active Transport, Cell Nucleus; Animals; Diabetes Mellitus; Disease Models, Animal; Down-Regulation; Forkhead Box Protein O1; Forkhead Transcription Factors; Glucose; Glucose Clamp Technique; Glucose-6-Phosphatase; Glycogen; Hepatocyte Nuclear Factor 4; Insulin; Insulin Resistance; Liver; Male; Mice; Obesity; Phosphatidylinositol 3-Kinases; Phosphoenolpyruvate Carboxykinase (GTP); Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Physical Exertion; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; Swimming

The current study showed that the daily oral treatment of fenugreek steroids, designated F(steroids), to diabetic rats during 30 days demonstrated a significant (p < 0.05) decrease of blood glucose level and a considerable increase of the area of insulin-immunoreactive beta-cells in diabetic rats. Interestingly, this study showed that F(steroids) potentially unregulated the key steroidogenesis enzymes such as 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), malic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and glucose-6-phosphate dehydrogenase (G6P-DH) activities as cholesterol rate in testis, which considerably enhanced testosterone and estradiol levels in the plasma of surviving diabetic rats. More interestingly, F(steroids) obviously prevented the alteration of the key carbohydrate enzymes such as hexokinase and pyruvate kinase activities as well as testicular glycogen and seminal fructose contents in surviving diabetic rats. Furthermore, F(steroids) administration to surviving diabetic rats significantly decreased the sperm shape abnormality and improved the sperm count. Above all, the potential protective action of reproductive systems was approved by the histological study of testis and epididymis.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Epididymis; Estradiol; Fructose; Glycogen; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Rats; Semen; Sperm Count; Spermatozoa; Steroids; Survival Rate; Testis; Testosterone; Time Factors; Trigonella

Cassia auriculata traditionally has been used to treat diabetes from ancient times. The objective of the present study was to investigate the mechanism of action for the antidiabetic activity of aqueous leaf extract of C. auriculata (CLEt) in streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) rats. CLEt was orally administered to MD and SD rats at a dose of 400 mg/kg once a day for 15 days. CLEt-treated MD and SD rats showed significant reduction in fasting blood glucose. Assessment of plasma insulin and C-peptide following treatment with CLEt revealed significant elevation in their levels. Administration of CLEt enhanced the activity of hepatic hexokinase and phosphofructokinase and suppressed glucose-6-phosphatase and fructose-1,6-bisphosphatase in both MD and SD rats. A significant rise in glycogen content was also observed in both liver and muscles of CLEt-fed MD and SD rats. Histopathological examination of pancreatic sections revealed increased number of islets and beta-cells in CLEt-treated MD as well as SD rats. The findings of the study suggest that the antidiabetic effect of CLEt could be due to its insulinogenic action. In addition, impaired glucose homeostasis was improved by feeding the extract through amelioration in the carbohydrate metabolic pathways. Thus, the extract may exert an antidiabetic effect through pancreatic as well as extrapancreatic action.

Topics: Animals; Blood Glucose; C-Peptide; Cassia; Diabetes Mellitus; Disease Models, Animal; Glucose; Glycogen; Humans; Hypoglycemic Agents; Insulin; Liver; Male; Muscle, Skeletal; Plant Extracts; Plant Leaves; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Streptozocin

Topics: Active Transport, Cell Nucleus; Animals; Diabetes Mellitus; Disease Models, Animal; Down-Regulation; Forkhead Box Protein O1; Forkhead Transcription Factors; Glucose; Glucose Clamp Technique; Glucose-6-Phosphatase; Glycogen; Hepatocyte Nuclear Factor 4; Insulin; Insulin Resistance; Liver; Male; Mice; Obesity; Phosphatidylinositol 3-Kinases; Phosphoenolpyruvate Carboxykinase (GTP); Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Physical Exertion; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; Swimming

In a previous study, we showed that a synthetic human insulin 1-chain analog, named analog (3) was capable of mimicking in vitro effects of native insulin, including stimulation of cell proliferation, glucose uptake and glycogen synthesis. Here, we have synthesized three new analogs (6, 9, 12) of the human A-chain, bearing or not their N- or C-terminal residue, to determine the structural features which are responsible for their biological properties. In vitro experiments clearly demonstrated that the N-terminal part of the peptides is required for the biological activity of the molecules, suggesting its crucial role in the mechanism underlying the cellular effect. Our findings may help to better understand the mechanism of interaction between insulin and its receptor. In addition, the present data demonstrate that some mini-insulin derived from the A-chain can exert similar effects as native insulin. These small peptides may offer specific advantages over insulin in the definition of new strategies for diabetes treatment.

Topics: Adipocytes; Analysis of Variance; Cell Line; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Diabetes Mellitus; Fibroblasts; Glucose; Glycogen; Humans; Insulin; Oligopeptides; Peptides; Structure-Activity Relationship

Measurement of plasma C2 glucose enrichment is cumbersome. Therefore, the plasma C5 glucose-to-(2)H(2)O rather than the plasma C5-to-C2 glucose ratio commonly has been used to measure gluconeogenesis and glycogenolysis during hyperinsulinemic-euglycemic clamps. The validity of this approach is unknown.. Ten nondiabetic and 10 diabetic subjects ingested (2)H(2)O the evening before study. The following morning, insulin was infused at a rate of 0.6 mU . kg(-1) . min(-1) and glucose was clamped at approximately 5.3 mmol/l for 5 h. Plasma C5 glucose, C2 glucose, and (2)H(2)O enrichments were measured hourly from 2 h onward.. Plasma C2 glucose and plasma (2)H(2)O enrichment were equal in both groups before the clamp, resulting in equivalent estimates of gluconeogenesis and glycogenolysis. In contrast, plasma C2 glucose and plasma C5 glucose enrichments fell throughout the clamp, whereas plasma (2)H(2)O enrichment remained unchanged. Since the C5 glucose concentration and, hence, the C5 glucose-to-(2)H(2)O ratio is influenced by both gluconeogenesis and glucose clearance, whereas the C5-to-C2 glucose ratio is only influenced by gluconeogenesis, the C5 glucose-to-(2)H(2)O ratio overestimated (P < 0.01) gluconeogenesis during the clamp. This resulted in biologically implausible negative (i.e., calculated rates of gluconeogenesis exceeding total endogenous glucose production) rates of glycogenolysis in both the nondiabetic and diabetic subjects.. Plasma C5 glucose-to-(2)H(2)O ratio does not provide an accurate assessment of gluconeogenesis in nondiabetic or diabetic subjects during a traditional (i.e., 2-3 h) hyperinsulinemic-euglycemic clamp. The conclusions of studies that have used this approach need to be reevaluated.

Topics: Blood Glucose; Deuterium Oxide; Diabetes Mellitus; Glucagon; Gluconeogenesis; Glucose Clamp Technique; Glycogen; Human Growth Hormone; Humans; Hyperinsulinism; Infusions, Intravenous; Insulin; Kinetics; Reference Values; Reproducibility of Results; Somatostatin; Water

Recent studies have identified the involvement of inhibitor IkappaB kinase (IKK) in the pathogenesis of insulin resistance. To investigate the mechanism involved, we examined the role of nuclear factor kappaB (NF-kappaB), the distal target of IKK, in hepatic glucose metabolism.. To inhibit NF-kappaB activity, db/db mice were infected with adenovirus expressing the IkappaBalpha super-repressor.. The IkappaBalpha super-repressor adenovirus infection caused a moderate reduction of NF-kappaB activity in liver. The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin-stimulated phosphorylation of Akt. On the other hand, quantification of mRNA in the liver revealed marked reduction of expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, concurrent with reduced expression of gene encoding peroxisome proliferator-activated receptor gamma coactivator-1alpha (PPARGC1A, also known as PGC-1alpha). Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection.. Our results indicate that moderate inhibition of NF-kappaB improved glucose tolerance through decreased gluconeogenesis associated with reduced PGC-1alpha gene expression in db/db mice, and suggest that inhibition of NF-kappaB activity in liver is a potentially suitable strategy for the normalisation of blood glucose concentration in type 2 diabetes.

Topics: Adenoviridae; AMP-Activated Protein Kinases; Animals; Cyclic AMP Response Element-Binding Protein; Diabetes Mellitus; Disease Models, Animal; Female; Glucose; Glycogen; I-kappa B Proteins; Insulin Resistance; Liver; Mice; Mice, Inbred C57BL; Multienzyme Complexes; NF-kappa B; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Serine-Threonine Kinases; STAT3 Transcription Factor; Trans-Activators; Transcription Factors; Triglycerides

An investigation was made to reveal the possible involvement of thyroid hormones in the progression of diabetes mellitus in response to an atherogenic diet; CCT (4% cholesterol, 1% cholic acid and 0.5% 2-thiouracil). Following the intake of CCT diet for 14 consecutive days a decrease in the serum levels of insulin, both the thyroid hormones, triiodothyronine (T(3)) and thyroxine (T(4)); hepatic glycogen content, hepatic type-1 iodothyronine 5'-mono-deiodinase (5'D) and serum alpha-amylase activities were observed, while there was an increase in the levels of serum glucose and nitrite and in lipid peroxidation of heart, liver and kidney tissues as well as in serum. However, simultaneous administration of L-thyroxine (500 microg/kg/day, s.c.) to CCT-diet fed animals resulted in the amelioration of all the aforesaid adverse changes including that of serum glucose, insulin, alpha-amylase, hepatic glycogen content and nitrite levels, suggesting the involvement of thyroid hormones in the progression of CCT-diet induced diabetes mellitus.

Topics: alpha-Amylases; Animals; Cholesterol; Creatine Kinase, MB Form; Diabetes Mellitus; Diet, Atherogenic; Glycogen; Hypothyroidism; Insulin; Iodide Peroxidase; Kidney; Lipid Peroxidation; Liver; Male; Myocardium; Nitrites; Rats; Rats, Wistar; Thyroxine; Triiodothyronine

Using an expression cloning strategy, we have identified TFE3, a basic helix-loop-helix protein, as a transactivator of metabolic genes that are regulated through an E-box in their promoters. Adenovirus-mediated expression of TFE3 in hepatocytes in culture and in vivo strongly activated expression of IRS-2 and Akt and enhanced phosphorylation of insulin-signaling kinases such as Akt, glycogen synthase kinase 3beta and p70S6 kinase. TFE3 also induced hexokinase II (HK2) and insulin-induced gene 1 (INSIG1). These changes led to metabolic consequences, such as activation of glycogen and protein synthesis, but not lipogenesis, in liver. Collectively, plasma glucose levels were markedly reduced both in normal mice and in different mouse models of diabetes, including streptozotocin-treated, db/db and KK mice. Promoter analyses showed that IRS2, HK2 and INSIG1 are direct targets of TFE3. Activation of insulin signals in both insulin depletion and resistance suggests that TFE3 could be a therapeutic target for diabetes.

Topics: Adenoviridae; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Blood Glucose; Blotting, Northern; Cells, Cultured; Chromatin Immunoprecipitation; Cloning, Molecular; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Green Fluorescent Proteins; Hepatocytes; Hexokinase; Humans; Immunoblotting; Immunoprecipitation; Insulin; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Phosphoproteins; Phosphorylation; Plasmids; Promoter Regions, Genetic; Protein Structure, Tertiary; Proto-Oncogene Proteins c-akt; Rats; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Streptozocin; Time Factors; Transcriptional Activation

Activation of inflammatory pathways may contribute to the beginning and the progression of both atherosclerosis and type 2 diabetes. Here we report a novel interaction between insulin action and control of inflammation, resulting in glucose intolerance and vascular inflammation and amenable to therapeutic modulation. In insulin receptor heterozygous (Insr+/-) mice, we identified the deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond between glucose intolerance and vascular inflammation. Among Insr+/- mice, those that develop diabetes have reduced Timp3 and increased TACE activity. Unchecked TACE activity causes an increase in levels of soluble TNF-alpha, which subsequently promotes diabetes and vascular inflammation. Double heterozygous Insr+/-Timp3+/- mice develop mild hyperglycemia and hyperinsulinemia at 3 months and overt glucose intolerance and hyperinsulinemia at 6 months. A therapeutic role for Timp3/TACE modulation is supported by the observation that pharmacological inhibition of TACE led to marked reduction of hyperglycemia and vascular inflammation in Insr+/- diabetic mice, as well as by the observation of increased insulin sensitivity in Tace+/- mice compared with WT mice. Our results suggest that an interplay between reduced insulin action and unchecked TACE activity promotes diabetes and vascular inflammation.

Topics: Analysis of Variance; Animals; Deoxyglucose; Diabetes Mellitus; Electrophoresis, Polyacrylamide Gel; Gene Expression Profiling; Genetic Vectors; Glucose; Glucose Tolerance Test; Glycogen; Heterozygote; Homeostasis; Hyperglycemia; Hyperinsulinism; Inflammation; Insulin; Liver; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Skeletal; Muscles; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Receptor, Insulin; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Time Factors; Tissue Inhibitor of Metalloproteinase-3; Tumor Necrosis Factor-alpha

A 2-year-did ferret was referred with a diagnosis of diabetes mellitus. The animal died despite insulin therapy and was submitted for necropsy. Light microscopic examination revealed a mild hepatic lipidosis and pancreatic lesions consisting of a diffuse vacuolation of the Langerhans' islet cells with a periodic acid-Schiff positive material compatible with glycogen.

Topics: Animals; Diabetes Mellitus; Fatal Outcome; Female; Ferrets; Glycogen; Hypoglycemic Agents; Insulin; Islets of Langerhans; Pancreas; Periodic Acid-Schiff Reaction; Vacuoles

The challenge of accurately predicting human clinical outcome based on preclinical data has led to a high failure rate of compounds in human clinical trials. A series of methods are described by which biosimulation can address these challenges and guide the design and evaluation of experimental and clinical protocols. Early compound development often proceeds on the basis of preclinical data from animal models. The systematic evaluation possible in a simulation can assist in the critical step of translating the preclinical outcomes to human physiology. Later in the process, clinical trials definitively establish a therapy's beneficial effects, as well as any adverse side effects. Biosimulation allows for the optimal design of clinical trials to ensure that key issues are addressed effectively and efficiently, and in doing so, improves the success rate of the trials.

Topics: Animals; Biological Assay; Clinical Trials as Topic; Computer Simulation; Diabetes Mellitus; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Drug Industry; Glycogen; Humans; Insulin; Liver; Male; Models, Biological; Rats; Rats, Wistar; Research Design; Species Specificity

Cardiac dysfunction is a severe secondary effect of Type 2 diabetes. Recruitment of the protein kinase B/glycogen synthase kinase-3 pathway represents an integral event in glucose homeostasis, albeit its regulation in the diabetic heart remains undefined. Thus the following study tested the hypothesis that the regulation of protein kinase B/glycogen synthase kinase-3 was altered in the myocardium of the Zucker diabetic fatty rat. Second, exercise has been shown to improve glucose homeostasis, and, in this regard, the effect of swimming training on the regulation of protein kinase B/glycogen synthase kinase-3 in the diabetic rat heart was examined. In the sedentary Zucker diabetic fatty rats, glucose levels were elevated, and cardiac glycogen content increased, compared with wild type. A 13-wk swimming regimen significantly reduced plasma glucose levels and cardiac glycogen content and partially normalized protein kinase B-serine473, protein kinase B-threonine308, and glycogen synthase kinase-3alpha phosphorylation in Zucker diabetic fatty rats. In conclusion, hyperglycemia and increased cardiac glycogen content in the Zucker diabetic fatty rats were associated with dysregulation of protein kinase B/glycogen synthase kinase-3 phosphorylation. These anomalies in the Zucker diabetic fatty rat were partially normalized with swimming. These data support the premise that exercise training may protect the heart against the deleterious consequences of diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glycogen; Glycogen Synthase Kinase 3; Heart Ventricles; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Hyperglycemia; Insulin; Male; Muscle, Skeletal; Myocardium; Phosphofructokinases; Phosphorylation; Physical Conditioning, Animal; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Zucker; Swimming

Hepatic glucose fluxes and intracellular movement of glucokinase (GK) in response to increased plasma glucose and insulin were examined in 10-wk-old, 6-h-fasted, conscious Zucker diabetic fatty (ZDF) rats and lean littermates. Under basal conditions, plasma glucose (mmol/l) and glucose turnover rate (GTR; micromol.kg(-1).min(-1)) were slightly higher in ZDF (8.4 +/- 0.3 and 53 +/- 7, respectively) than in lean rats (6.2 +/- 0.2 and 45 +/- 4, respectively), whereas plasma insulin (pmol/l) was higher in ZDF (1,800 +/- 350) than in lean rats (150 +/- 14). The ratio of hepatic uridine 5'-diphosphate-glucose 3H specific activity to plasma glucose 3H specific activity ([3H]UDP-G/[3H]G; %), total hepatic glucose output (micromol.kg(-1).min(-1)), and hepatic glucose cycling (micromol.kg(-1).min(-1)) were higher in ZDF (35 +/- 5, 87 +/- 16, and 33 +/- 10, respectively) compared with lean rats (18 +/- 3, 56 +/- 6, and 11 +/- 2, respectively). [3H]glucose incorporation into glycogen (micromol glucose/g liver) was similar in lean (1.0 +/- 0.7) and ZDF (1.6 +/- 0.8) rats. GK was predominantly located in the nucleus in both rats. With elevated plasma glucose and insulin, GTR (micromol.kg(-1).min(-1)), [3H]UDP-G/[3H]G (%), and [3H]glucose incorporation into glycogen (micromol glucose/g liver) were markedly higher in lean (191 +/- 22, 62 +/- 3, and 5.0 +/- 1.4, respectively) but similar in ZDF rats (100 +/- 6, 37 +/- 3, and 1.4 +/- 0.4, respectively) compared with basal conditions. GK translocation from the nucleus to the cytoplasm occurred in lean but not in ZDF rats. The unresponsiveness of hepatic glucose flux to the rise in plasma glucose and insulin seen in prediabetic ZDF rats was associated with impaired GK translocation.

Topics: Animals; Biological Transport; Blood Glucose; Carrier Proteins; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon; Glucokinase; Glucose; Glucose-6-Phosphate; Glycogen; Insulin; Intracellular Membranes; Intracellular Signaling Peptides and Proteins; Liver; Male; Muscle, Skeletal; Obesity; Rats; Rats, Zucker; Thinness; Tissue Distribution

The contribution of increased gluconeogenesis (GNG) to the excessive rate of endogenous glucose production (EGP) in type 2 diabetes (T2DM) is well established. However, the separate effects of obesity (total body fat), visceral adiposity, and T2DM have not been investigated. We measured GNG (by the (2)H(2)O technique) and EGP (with 3-(3)H-glucose) after an overnight fast in 44 type 2 diabetic and 29 gender/ethnic-matched controls. Subjects were classified as obese (body mass index 30 kg/m(2) or greater) or nonobese (body mass index < 30 kg/m(2)); diabetic subjects were further subdivided according to the severity of fasting hyperglycemia [fasting plasma glucose (FPG) < 9 mm or >or= 9 mm]. EGP was similar in nondiabetic controls and T2DM with FPG less than 9 mm but was increased in T2DM with FPG >or= 9 mm (P < 0.001). Within the diabetic groups, obesity had an independent effect to further increase basal EGP (P < 0.01). In both nonobese diabetic groups, both the percent GNG and gluconeogenic flux were increased, compared with nonobese nondiabetic controls. In both diabetic groups, obesity further increased both percent GNG and gluconeogenic flux. In obese and nonobese T2DM, the increase in gluconeogenic flux was not accompanied by a reciprocal decrease in glycogenolysis, indicating a loss of hepatic autoregulation. By multivariate analysis, gluconeogenic flux was positively correlated with percent body fat, visceral fat, and the fasting plasma free fatty acid and glucose concentrations (all P

Topics: Abdomen; Adipose Tissue; Adult; Anthropometry; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Gluconeogenesis; Glucose; Glucose Clamp Technique; Glycogen; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Obesity

Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

Topics: Amino Acid Sequence; Animals; Cell Fractionation; Cell Membrane; Cell Nucleus; Diabetes Mellitus; Gene Expression; Gerbillinae; Glucose; Glycogen; Insulin; Liver; Membrane Proteins; Microsomes, Liver; Mitochondria, Liver; Molecular Sequence Data; Obesity; Peptide Fragments; Phosphoenolpyruvate Carboxykinase (GTP); Phosphorylation; Receptor, Insulin; Transfection; Triglycerides; Tumor Cells, Cultured

Agonists of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) are pharmacologically active antihyperglycemic agents that act by increasing peripheral tissue sensitivity to insulin. Many of these agonists have antihyperglycemic activity that is directly proportional to their ability to bind and activate PPAR gamma; however, recent data bring this relationship into question. In this report we describe a new PPAR gamma agonist, CLX-0921, that is derived from a natural product. This thiazolidinedione (TZD) has a spectrum of activity that differs from commercially available TZDs. It is a weak activator of PPAR gamma (EC(50) of 0.284 micromol/L) compared to rosiglitazone (EC(50) 0.009 micromol/L). Despite this difference, the drug maintains potent glucose uptake activity in vitro and glucose-lowering activity in vivo that is equipotent to that of rosiglitazone. Moreover, CLX-0921 showed a 10-fold reduction in in vitro adipogenic potential compared to rosiglitazone. CLX-0921 also increases glycogen synthesis, an activity not typically associated with rosiglitazone or pioglitazone. Thus CLX-0921 appears to have a distinct spectrum of activity relative to other TZDs.

Topics: 3T3 Cells; Adipocytes; Adipose Tissue; Animals; Blood Glucose; Cells, Cultured; Diabetes Mellitus; Dose-Response Relationship, Drug; Glycogen; Humans; Hypoglycemic Agents; Insulin; Mice; Mice, Inbred C57BL; Mice, Obese; Radioligand Assay; Rats; Rats, Zucker; Receptors, Cytoplasmic and Nuclear; Rosiglitazone; Thiazoles; Thiazolidinediones; Transcription Factors; Transcriptional Activation; Transfection

Lipid accumulation in nonadipose tissues is closely related to the development of type 2 diabetes in obese subjects. We examined the potential preventive effect of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma stimulation on the development of diabetes in obese diabetes-prone OLETF rats. Chronic administration of a PPAR-alpha agonist (0.5% [wt/wt] fenofibrate) or a PPAR-gamma agonist (3 mg x kg(-1) x day(-1) rosiglitazone) completely prevented the development of glycosuria. Pancreatic islets from untreated OLETF rats underwent sequential hypertrophy and atrophy, which was completely prevented by chronic fenofibrate treatment. In contrast, rosiglitazone treatment did not affect islet hypertrophy at earlier stages but prevented beta-cell atrophy at later stages. Fenofibrate treatment decreased body weight and visceral fat, whereas rosiglitazone treatment increased body weight. Despite the opposite effects on adiposity, both drugs were equally effective in improving insulin actions in skeletal muscle. Furthermore, both drugs significantly decreased the triglyceride content in the soleus muscle and pancreatic islets. The present study demonstrates that the PPAR-alpha agonist fenofibrate prevents the development of diabetes in OLETF rats by reducing adiposity, improving peripheral insulin action, and exerting beneficial effects on pancreatic beta-cells.

Topics: Adipose Tissue; Animals; Basal Metabolism; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids; Fenofibrate; Glycogen; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Islets of Langerhans; Male; Muscle, Skeletal; Obesity; Rats; Rats, Inbred OLETF; Receptors, Cytoplasmic and Nuclear; Rosiglitazone; Thiazoles; Thiazolidinediones; Transcription Factors; Triglycerides; Viscera

The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.. Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days.. Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal.. The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.

Topics: Aminoimidazole Carboxamide; Animals; Biological Transport; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose; Glucose Tolerance Test; Glycogen; Homeostasis; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Resistance; Liver; Liver Glycogen; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal; Obesity; Ribonucleotides

1. The effects of combined treatment with pioglitazone.HCl and metformin on diabetes and obesity were investigated in Wistar fatty rats, which are hyperglycaemic and hypertriglyceridaemic and have higher plasma levels of total ketone bodies than lean rats. 2. Plasma glucose was significantly decreased when pioglitazone.HCl or metformin was administered alone and combined treatment accentuated this decrease. The administration of pioglitazone.HCl, but not metformin, also decreased plasma levels of triglyceride and total ketone bodies. 3. The glycogen content of skeletal muscle was not increased by pioglitazone.HCl or metformin alone, but was increased by combined treatment (P=0.003, ANOVA). 4. Pioglitazone.HCl produced increased food intake and bodyweight in hyperphagic Wistar fatty rats; however, concurrent administration of metformin significantly ameliorated these pioglitazone.HCl-induced increases. 5. These results indicate that combined treatment with pioglitazone.HCl and metformin induces a marked hypoglycaemic effect accompanied by a reduction in plasma levels of total ketone bodies and prevention of excessive bodyweight gain in Wistar fatty rats. These favourable effects suggest that the combination would be beneficial in treating patients with type 2 diabetes.

Topics: Adipose Tissue; Animals; Body Weight; Diabetes Mellitus; Drug Therapy, Combination; Eating; Glycogen; Hypoglycemic Agents; Ketone Bodies; Liver; Male; Metformin; Muscle, Skeletal; Obesity; Organ Size; Pioglitazone; Rats; Rats, Wistar; Thiazoles; Thiazolidinediones

Although lipid excess can impair beta-cell function in vitro, short-term high-fat feeding in normal rats produces insulin resistance but not hyperglycemia. This study examines the effect of long-term (10-mo) high polyunsaturated fat feeding on glucose tolerance in Wistar rats. The high fat-fed compared with the chow-fed group was 30% heavier and 60% fatter, with approximately doubled fasting hyperinsulinemia (P < 0.001) but only marginal fasting hyperglycemia (7.5 +/- 0.1 vs. 7.2 +/- 0.1 mmol/l, P < 0.01). Insulin sensitivity was approximately 67% lower in the high-fat group (P < 0.01). The acute insulin response to intravenous arginine was approximately double in the insulin-resistant high-fat group (P < 0.001), but that to intravenous glucose was similar in the two groups. After the intravenous glucose bolus, plasma glucose decline was slower in the high fat-fed group, confirming mild glucose intolerance. Therefore, despite severe insulin resistance, there was only a mildly elevated fasting glucose level and a relative deficiency in glucose-stimulated insulin secretion; this suggests that a genetic or congenital susceptibility to beta-cell impairment is required for overt hyperglycemia to develop in the presence of severe insulin resistance.

Topics: Acyl Coenzyme A; Aging; Animals; Arginine; Blood Glucose; Body Composition; Diabetes Mellitus; Dietary Fats; Fasting; Genetic Predisposition to Disease; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Glycogen; Insulin; Insulin Resistance; Liver; Male; Muscle, Skeletal; Rats; Rats, Wistar; Time Factors; Triglycerides; Weight Gain

Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl). The animals became normoglycemic for approximately 10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at approximately 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 +/- 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liver-pyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity.

Topics: Administration, Oral; Animals; Diabetes Mellitus; Glucose-6-Phosphate; Glycogen; Hyperglycemia; Hypoglycemic Agents; Islets of Langerhans; Liver; Male; Obesity; Phosphorylation; Rats; Rats, Zucker; Tungsten Compounds; Tyrosine

Insulin resistance of skeletal muscle has been associated with increased lipid availability. This study aimed to estimate volume fractions of intramyocellular triglyceride droplets and glycogen granules in skeletal muscle using electron microscopy and furthermore, relate these findings to insulin sensitivity and the level of circulating lipids.. We compared 11 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 11 obese normoglycaemic subjects matched for age and sex. Glucose metabolism was determined using the euglycaemic hyperinsulinaemic clamp technique (40 mU.m(-2).min(-1)) coupled with indirect calorimetry and tritiated glucose. On the second day, using an automatic procedure, a fasting muscle biopsy was carried out and processed for electron microscopy. Volume fractions of intramyocellular structures were estimated by pointcounting on photographic pictures in a blinded manner.. Insulin-stimulated total glucose disposal rate was lower in the Type II diabetic subjects compared with the obese normoglycaemic subjects (4.96 +/- 049 vs 10.35 +/- 0.89 mg.min(-1).kg ffm(-1), p < 0.001) as was glucose storage (2.03 +/- 0.50 vs 6.59 +/- 0.83, p < 0.001). The electron microscopy study revealed that the diabetic subjects had higher intramyocellular amounts of triglyceride (1.43 +/- 0.21 vs 0.39 +/- 0.07%, p < 0.001) and lower amounts of glycogen (3.53 +/- 0.33 vs 6.94 +/- 0.54%, p < 0.001). Mitochondrial volume was identical indicating equal aerobic capacity. The fractional intramyocellular lipid volume was found to be positively associated with fasting NEFA (r = 0.63, p = < 0.05 and r = 0.79, p = < 0.05) and triglyceride (r = 0.74, p = 0.01 and r = 0.62, p < 0.05) in the obese diabetic and normoglycaemic cohorts respectively. Intramyocellular lipid content was negatively correlated to insulin sensitivity (r = -0.71, p < 0.02) in the obese diabetic group whereas no significant association was found in the obese normoglycaemic group.. This study shows that fat accumulates intramyocellulary while glycogen stores are simultaneously reduced in obese subjects with Type II (non-insulin-dependent) diabetes mellitus. Quantitatively, a major component of the excessive lipid accumulation could be secondary in origin, related to the diabetic state in itself, although a contribution from the altered insulin action cascade of obesity and diabetes cannot be excluded. In both groups significant positive relations were found between circulating and intramyocellular lipid.

Topics: Adipocytes; Blood Glucose; Calorimetry, Indirect; Cholesterol; Cholesterol, HDL; Diabetes Mellitus; Fatty Acids, Nonesterified; Glucose Clamp Technique; Glucose Tolerance Test; Glycogen; Humans; Hyperinsulinism; Insulin Resistance; Lipid Metabolism; Middle Aged; Muscle, Skeletal; Obesity; Triglycerides; White People

Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage and disposal in the liver. GK levels are lowered in patients with maturity-onset diabetes of the young and in some diabetic animal models. Here, we explored the adenoviral vector-mediated overexpression of GK in a diet-induced murine model of type 2 diabetes as a treatment for diabetes. Diabetic mice were treated by intravenous administration with an E1/E2a/E3-deleted adenoviral vector encoding human hepatic GK (Av3hGK). Two weeks posttreatment, the Av3hGK-treated diabetic mice displayed normalized fasting blood glucose levels (95 +/- 4.8 mg/dl; P < 0.001) when compared with Av3Null (135 +/- 5.9 mg/dl), an analogous vector lacking a transgene, and vehicle-treated diabetic mice (134 +/- 8 mg/dl). GK treatment also resulted in lowered insulin levels (632 +/- 399 pg/ml; P < 0.01) compared with the control groups (Av3Null, 1,803 +/- 291 pg/ml; vehicle, 1,861 +/- 392 pg/ml), and the glucose tolerance of the Av3hGK-treated diabetic mice was normalized. No significant increase in plasma or hepatic triglycerides, or plasma free fatty acids was observed in the Av3hGK-treated mice. These data suggest that overexpression of GK may have a therapeutic potential for the treatment of type 2 diabetes.

Topics: Adenoviridae; Animals; Blood Glucose; Diabetes Mellitus; Eating; Fasting; Gene Expression; Gene Transfer Techniques; Genetic Vectors; Glucokinase; Glycogen; Humans; Insulin; Liver; Male; Mice; Mice, Inbred C57BL; Phenotype; Triglycerides

Topics: Diabetes Mellitus; Glycogen; History, 19th Century; History, 20th Century; Humans; Insulin; Nobel Prize

The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge.. Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast.. The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak.. It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.

Topics: Adipose Tissue; Adult; Blood Glucose; Calorimetry, Indirect; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Exercise; Glucose Tolerance Test; Glycogen; Humans; Insulin; Male; Muscle, Skeletal; Obesity; Oxygen Consumption; Physical Exertion; Triglycerides

Increased endogenous glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C fructose (0.3 g.kg fat free mass-1.h-1) for 3 h. Fructose failed to increase EGP (measured with 6,6 2H glucose) in NIDDM (17.7 +/- 1.9 mumol.kg fat free mass-1.min-1 basal vs 15.9 +/- 0.9 after fructose), in obese non-diabetic subjects (12.1 +/- 0.5 basal vs 13.1 +/- 0.5 after fructose) and in lean healthy subjects (13.3 +/- 0.5 basal vs 13.8 +/- 0.6 after fructose) although 13C glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13C fructose ingestion + hyperglucagonaemia (232 +/- 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of fructose + glucagon (p < 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i.e. glycogenolysis + gluconeogenesis from non-fructose precursors).

Topics: Administration, Oral; Adult; Analysis of Variance; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Female; Fructose; Glucagon; Gluconeogenesis; Glucose; Glycogen; Humans; Infusions, Intravenous; Kinetics; Male; Middle Aged; Models, Theoretical; Obesity; Reference Values

The frequent development of Type 2 diabetes in the obese suggests a relationship between obesity and diabetes. This study presents evidence for a continuum form obesity to diabetes via glucose intolerance and hyperinsulinemic diabetes. The defect which seems to be at the origin of this development resides in the increase in lipid oxidation already present in the early stages of obesity. It reflects the increased utilisation of fatty acids for energy purpose in the obese, at the expenses of glucose. In non-diabetic obese subjects, insulin resistance can be demonstrated by the inhibition of glucose storage during a euglycemic, hyperinsulinemic, clamp. This defect in glucose storage is not observed during a oral glucose tolerance test (OGTT), as it is compensated by hyperinsulinemia and hyperglycemia during glucose tolerance. Glucose tolerance appears with the inhibition of glucose oxidation by the augmented lipid oxidation. This decreased glucose utilization causes a slowdown of the utilization of glycogen stores which leads, as a consequence, to the inhibition of glycogen synthase by its product, glycogen. Diabetes appears when the increase in glycemia and insulinemia does not compensate any more for the inhibition of glucose storage. The rise in basal glycemia simultaneously with the fall in glucose storage corresponds to the transition to diabetes. The decreased glucose mobilization together with the inhibition of glycogen phosphorylase are such in the diabetic patient that glycogen stores tend to remain full and glycogen synthase is inhibited by negative feedback. The retrograde inhibition of glycogen stores on glycogen synthase activity brings up incapacity to store glucose and leads to a rise in glycemia. Finally, the evolution of obesity to diabetes leads to a decrease in insulin secretion with increase in hepatic glucose production through gluconeogenesis and decreased capacity to store glucose. Therapeutic implications are discussed in this review.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Acids; Glucose; Glycogen; Humans; Insulin; Liver; Middle Aged; Muscles; Obesity

Glycogenated hepatocyte nuclei are a common finding in liver biopsy specimens from patients presenting with a variety of clinical disorders. Most commonly, glycogenated nuclei from part of a spectrum of pathological changes in the diabetic or obese patient. However, no previous investigation has assessed glycogenated hepatocyte nuclei in a quantitative manner. In this study we used receiver operating characteristic (ROC) analysis to assess quantitatively the strength of glycogenated nuclei as a marker for diabetes and/or obesity. The study population consisted of 102 liver biopsy specimens from the adult population: 20 from diabetic patients, 41 from obese patients, 10 from both obese and diabetic patients, and 31 from neither diabetic nor obese patients. The mean age was 48.5 years with a range of 18 to 80 years. We evaluated the extent of glycogenated nuclei by averaging the number present per high power field over a minimum of 10 high power fields, representing all zones of the liver. The extent of steatosis was graded on a numerical scale from 1 to 10. In ROC analysis perfect tests are associated with an area of 1.0 and completely random tests with an area of 0.5. Receiver operating characteristic analysis showed that glycogenated nuclei are a relatively good test for distinguishing diabetic from nondiabetic patients (area, 0.75), a poor test for distinguishing obese from nonobese patients (area, 0.60), and a fair test for either condition (area, 0.67). In addition, we observed that glycogenated nuclei were preferentially distributed in the periportal "zone 1" of the liver, showed no correlation with steatosis, and had no relation to patient age. For our patient study population the prevalence of diabetes mellitus was 12%. At a cutoff level of four glycogenated nuclei per 400 x high power field, the specificity and sensitivity of glycogenated nuclei as a test for diabetes are 0.98 and 0.30, respectively, with a positive predictive value of 66%.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biopsy; Cell Nucleus; Diabetes Mellitus; Female; Glycogen; Humans; Liver; Male; Middle Aged; Obesity; ROC Curve

Skeletal muscle contributes significantly to reduced insulin-stimulated glucose disposal in patients with obesity and non-insulin-dependent (type II) diabetes mellitus (NIDDM). The biochemical basis for insulin resistance is not known but may involve reduced glucose transport and/or a defect in intracellular pathways for glucose disposal. To address this question, we measured basal and insulin-stimulated glucose oxidation, glycogen formation, and nonoxidative glycolysis (lactate and amino acid release) in an incubated muscle preparation from nonobese and morbidly obese patients with and without NIDDM. Pathways of glucose disposal were also determined in muscle of obese NIDDM patients incubated under hyperglycemic (20 mmol/L) conditions, which increases glucose uptake by mass action. Under basal conditions (no insulin present) there were no significant differences in glycogen formation or glucose oxidation between nonobese control, obese nondiabetic, or obese diabetics. Lactate release was significantly higher in obese controls compared to nonobese controls in the basal state at 5 mmol/L glucose (10.2 +/- 2.8 v 24.7 +/- 3.5 nmol/min/g, P < .05). Under maximal insulin-stimulated conditions, rates of glycogen formation, glucose oxidation, and nonoxidized glycolysis increased 1.9-, 2.3-, and 2.2-fold over basal (P < .05) in nonobese controls. By contrast, insulin was ineffective at stimulating significant increases in any metabolic pathway of glucose disposal in muscle of obese or obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Analysis of Variance; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose; Glycogen; Glycolysis; Humans; In Vitro Techniques; Insulin; Male; Middle Aged; Muscles; Obesity; Obesity, Morbid; Oxidation-Reduction

Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.

Topics: Adult; Chorion; Diabetes Mellitus; Female; Glucose; Glycogen; Glycogen Synthase; Glycoproteins; Humans; Hydatidiform Mole; Oligosaccharides; Phosphorylases; Placenta; Polysaccharides; Pre-Eclampsia; Pregnancy; Trophoblasts

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus; Female; Glycogen; Humans; Male; Middle Aged

The present study describes the structural changes in the gracile nucleus of the spontaneously diabetic BB rat. At 3-7 days post-diabetes, axons, axon terminals and dendrites showed electron-dense degeneration. Degenerating axons were characterized by swollen mitochondria, vacuolation, accumulation of glycogen granules, tubulovesicular elements, neurofilaments and dense lamellar bodies. Degenerating axon terminals consisted of an electron-dense cytoplasm containing swollen mitochondria, vacuoles and clustering of synaptic vesicles. These axon terminals made synaptic contacts with cell somata, dendrites and other axon terminals. Degenerating dendrites were postsynaptic to normal as well as degenerating axon terminals. At 1-3 months post-diabetes, degenerating electron-dense axons, axon terminals and dendrites were widely scattered in the neuropil. Macrophages containing degenerating electron-dense debris were also present. At 6 months post-diabetes, the freshly degenerating neuronal elements encountered were similar to those observed at 3-7 days. However, there were more degenerating profiles at 6 months post-diabetes compared to the earlier time intervals. Terminally degenerating axons were vacuolated and their axoplasm appeared amorphous. It is concluded that degenerative changes occur in the gracile nucleus of the spontaneously diabetic BB rat.

Topics: Animals; Axons; Brain Stem; Diabetes Mellitus; Disease Models, Animal; Glycogen; Intermediate Filaments; Male; Mitochondrial Swelling; Rats; Rats, Inbred BB; Vacuoles

The effect of long-term (12 weeks) oral treatment with sodium orthovanadate on hepatic glycogen metabolizing and lipogenic enzymes was studied in genetically diabetic db/db mice. These mice were characterized by significant (P less than .001) obesity, hyperglycemia, and hyperinsulinemia. Vanadate administration led to significant decreases in body weight (P less than .001) and plasma insulin levels (P less than .01) and the mice became normoglycemic. The total glycogen synthase (EC 2.4.1.11) activity in the livers of diabetic mice showed a 47% increase, which did not undergo any significant change after treatment with vanadate. Hepatic phosphorylase (EC 2.4.1.1) activities (a and total) showed twofold increases in db/db mice when compared with the nondiabetic ones. Vanadate caused significant decreases in phosphorylase a (P less than .02) and total phosphorylase (P less than .001) activities. Glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and malic enzyme (EC 1.1.1.40) in diabetic liver had differential alterations, as indicated by a 50% decrease in glucose-6-phosphate dehydrogenase and 160% increase in malic enzyme activities. Vanadate administration led to normalization of both enzyme activities. In nondiabetic mice, vanadate treatment did not cause changes in any parameter, except for a 46% decrease in plasma insulin levels. This investigation indicates that vanadate can normalize many of the metabolic abnormalities seen in the liver of genetically diabetic db/db mice, a model for non-insulin-dependent diabetes mellitus (NIDDM). Vanadate also causes a decrease in plasma insulin level, along with normalization of plasma glucose, which suggests a partial reversal of insulin resistance.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glucosephosphate Dehydrogenase; Glycogen; Glycogen Synthase; Insulin; Lipids; Liver; Mice; Mice, Inbred Strains; Time Factors; Vanadates

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Glycogen; Humans; Insulin; Islets of Langerhans

Topics: Adenosine Triphosphate; Allosteric Regulation; Carbohydrates; Diabetes Mellitus; Energy Metabolism; Gluconeogenesis; Glycogen; Glycolysis; Humans; Mitochondria; NADP; Phosphorylation; Tartrates; Uronic Acids

Topics: Catecholamines; Diabetes Mellitus; Energy Metabolism; Exercise Therapy; Glucose; Glycogen; Humans; Insulin; Physical Education and Training; Rest

Topics: Diabetes Mellitus; Energy Metabolism; Exercise; Glucose; Glycogen; Humans; Insulin; Muscles; Physical Education and Training

The preliminary results from integration-evaluation on a set of 310 binary relations in current data base of the new research Quantitatively Medicine Simulating and Operating by Computer (QMSOC) are presented in this paper. Through the function derived from the reciprocity in analysis of conditions, subjects and objects, in the given biomedical events, the number of routes for observation of glucagon and insulin was increased by 38.1% and 136.4% over the conventional object-oriented searching, respectively. The intersection operation of condition sets indicates that it is possible through QMSOC to increase markedly the degree of definity of causality of biomedical events. 70 new binary quantitative relations have been created through operator 1, achieving an increment of 22.6% over the total of original binary relations in the data base. The characteristics and the significance of QMSOC are discussed.

Topics: Causality; Computer Simulation; Diabetes Mellitus; Glycogen; Humans; Information Systems; Insulin

Topics: Diabetes Mellitus; Glycogen; Humans; Myocardial Infarction

In estimating glucose and fructose 6-phosphate futile cycling in vivo, complete detritiation of [2-3H]glucose is assumed at the glucose 6-phosphate level, [3-3H]glucose at triose phosphate formation, and [6-3H]glucose in its conversion to glucose via pyruvate. [3-3H]glucose detritiation via the pentose cycle is assumed to be negligible. Normal and non-insulin-dependent diabetic subjects, in the basal state and infused with glucose, were given [2-3H,2-14C]galactose, and 3H-to-14C ratios in blood glucose were determined. [2-3H,2-14C]glucose was given with acetaminophen, and 3H/14C in urinary glucuronide was determined. Detritiation at glucose 6-phosphate was approximately 80%. [3-3H,1-14C]fructose was infused, and 3H/14C was determined in blood glucose and urinary glucuronide. At triose phosphate, 75-90% of the 3H was removed. The pentose cycle contribution was only a few percent. [6-3H,6-14C]glucose was infused, and 3H/14C in blood lactate was determined. [3-3H,3-14C]lactate was infused, and ratios in blood glucose were determined. Maximally, 10% of 3H from [6-3H]glucose was retained. If glucose and galactose are metabolized in the same hepatic site(s), glucose conversion to three-carbon intermediates in the indirect pathway of glycogen formation occurs in extrahepatic tissue(s). Reported estimates of futile cycling, although qualitatively correct, quantitatively require correction.

Topics: Adult; Blood Glucose; Carbon Radioisotopes; Diabetes Mellitus; Fructosephosphates; Galactose; Glucose; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Humans; Liver; Male; Middle Aged; Pentose Phosphate Pathway; Tritium

A 30 year old man with DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) syndrome associated with myocardial disease is reported. Echocardiographic study revealed a marked symmetric left ventricular hypertrophy. Histology of the endomyocardial biopsy specimen from the right ventricle showed severe glycogen deposition in the myocytes. This case may indicate that DIDMOAD syndrome is a hereditary systemic disease affecting multiple organs, including the myocardium.

Topics: Adult; Cardiomyopathies; Deafness; Diabetes Complications; Diabetes Insipidus; Diabetes Mellitus; Endocardium; Glycogen; Humans; Male; Myocardium; Optic Atrophy; Syndrome

Phosphorylase and glycogen synthase protein were measured in normal and genetically diabetic (C57BL/KsJ db/db) mice liver extracts using rocket immunoelectrophoresis, and these data correlated with measurements of total phosphorylase and total glycogen synthase activities, respectively. Phosphorylase protein in 5-week-old normal mice was about 5 micrograms/mg protein and reached 8 micrograms/mg protein by 9 weeks. In comparison, the diabetic mice had elevated levels of phosphorylase protein (11-13 micrograms/mg protein) which correlated with an increased total phosphorylase activity compared to normals. The correlation coefficient for the phosphorylase activity vs protein plot was highly significant (r = 0.73, P less than 0.001). The molar concentration of phosphorylase subunit in normal mouse liver was calculated to be 11 microM and up to 23 microM in the diabetic mice. The liver concentration of glycogen synthase was relatively constant in normal mice at 400 ng/mg protein (corresponding to approximately 1.4 microM) but varied from 230 to 441 ng/mg protein (0.9 to 1.8 microM) in diabetic mice. There was little correlation between glycogen synthase activity and enzymatic protein (r = 0.15). These results indicate (1) that phosphorylase is present at concentrations approximately 10 times that of glycogen synthase, and (2) that glycogen synthase activity is relatively more dependent upon factors other than the amount of enzymatic protein.

Topics: Animals; Diabetes Mellitus; Glycogen; Glycogen Synthase; Immune Sera; Immunoelectrophoresis; Liver; Mice; Mice, Inbred C57BL; Molecular Weight; Muscles; Phosphorylases; Rabbits

Current knowledge about the thermic effects of exercise in lean and obese subjects and the relationships between exercise and food intake, resting metabolic rate, and dietary-induced thermogenesis were reviewed. Studies of the effects of carbohydrate restriction during low calorie diets on the capacity to perform physical exercise and of the effects of weight reduction with or without the addition of physical training on the metabolic abnormalities of non-insulin-dependent diabetes mellitus are also described. The metabolic efficiency of physical work is normal in obesity, total energy expenditure is increased because of increased body mass, and increased energy expenditure is not necessarily matched by a compensatory increase in caloric intake. Thus, increased physical activity can be expected to result in negative energy balance in obese subjects. It is not clear whether exercise increases resting metabolic rate, but there is considerable evidence that exercise may potentiate the thermic effect of food in lean subjects and that this response may be blunted in the obese. The capacity to perform moderate-intensity exercise during carbohydrate-restricted, low calorie diets is maintained after a period of adaptation, but the capacity for high-intensity exercise (greater than 70% VO2max) is decreased unless adequate carbohydrate is provided to maintain muscle glycogen stores. The major effect of the addition of a program of physical training to dietary restriction and weight reduction in the treatment of non-insulin-dependent diabetes mellitus is an increase in peripheral sensitivity to insulin, primarily due to increased non-oxidative glucose disposal in muscle tissue.

Topics: Animals; Basal Metabolism; Blood Glucose; Body Composition; Body Temperature Regulation; Body Weight; Diabetes Mellitus; Diet, Reducing; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Glucose Tolerance Test; Glycogen; Humans; Male; Muscles; Obesity; Physical Endurance; Physical Exertion; Rats; Time Factors

Cytochemical indices of leukocytes were determined in 16 patients with diabetes mellitus in the period of unbalancing and balancing. The following tests were made: content of glycogen and lipids, acid phosphatase (AP), alkaline phosphatase (AIP), myeloperoxidase (MPO) and nonspecific alpha-naphtol acetate esterase (NANAE) activity. In unbalanced diabetics an evident decrease in the activity of AP and MPO could be noted as well as a decrease of glycogen content and an increase of lipid content. An insignificant decrease could be observed in the activity of ALP and NANAE in granulocytes. A slight increase in the activity of NANAE in monocytes would be found. Balancing this disease induced the increase of all parameters in granulocytes except MPO activity. It is interesting to note that balancing diabetes mellitus deepened the observed changes in the decrease or increase of tested parameters. The presented findings clearly indicate the role of metabolic disorders in diabetes mellitus on the activity of some neutrophilic enzymes and the glycogen and the content of lipids in neutrophils.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Diabetes Mellitus; Female; Glycogen; Humans; Leukocytes; Lipids; Male; Middle Aged; Naphthol AS D Esterase; Peroxidase

Topics: Blood Glucose; Capillaries; Diabetes Mellitus; Gingiva; Glycogen; Humans

It has been reported that sand rats, naturally feeding on low-caloric-value plants containing a high concentration of salt, become obese and develop hyperglycemia when fed on a standard laboratory diet. The aim of this study was to examine the long-term effects of a synthetic-chow diet on the metabolic pattern of the diabetic syndrome in a large group of sand rats. While a few animals had a fulminant reaction with markedly decreased glucose tolerance, low plasma insulin levels, and death within 3-4 wk, most sand rats developed obesity and elevated plasma insulin levels. From the third month and forward, 40% of sand rats presented with a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance, and insulin resistance. This diabetic syndrome can be compared with maturity-onset (type II) diabetes. When this synthetic-chow diet was given for more than 6 mo, the majority of animals lost considerable weight and showed a major depletion of fat stores. Serum immunoreactive insulin levels fell, while blood glucose rose to above 500 mg/dl with glycosuria and ketonuria. The elevated triglyceride content of plasma and the lipid deposits in the liver were greatly augmented, and no glycogen was present. Animals developed frank insulin-dependent diabetes, and diabetic animals not treated with insulin died in diabetic coma with presumed ketoacidosis. The disease was essentially confined to sand rats showing abnormal glucose tolerance, even before eating laboratory chow. This observation suggests a genetic factor. Thus, the sand rat appears to be a potentially interesting model for investigation of both maturity-onset and insulin-dependent diabetes.

Topics: Animal Feed; Animals; Arvicolinae; Blood Glucose; Body Weight; Diabetes Mellitus; Disease Models, Animal; Energy Intake; Female; Glucose Tolerance Test; Glycogen; Glycosuria; Insulin; Ketone Bodies; Liver; Male

Topics: Blood Glucose; Diabetes Mellitus; Fatty Acids; Glucagon; Gluconeogenesis; Glucose; Glycogen; Humans; Insulin; Islets of Langerhans; Ketone Bodies; Liver

Topics: Adolescent; Adult; Diabetes Mellitus; Glycogen; Humans; Lymphocytes; Male; Periodic Acid-Schiff Reaction

Topics: Adult; Aged; Animals; Basement Membrane; Blood Glucose; Cornea; Corneal Diseases; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Edema; Epithelium; Female; Fructose; Glucose; Glycogen; Humans; Male; Middle Aged; Postoperative Complications; Rabbits; Rats; Sorbitol; Vitrectomy

In polymorphonuclear leukocytes from severely diabetic patients the rate of glycolysis is decreased due to decreased activity of phosphofructokinase, and the glycogen content and rate of glycogen synthesis are decreased due to a decreased total activity of glycogen synthase and an impaired activation of this enzyme. Covalent modification of glycogen synthase by phosphorylation creates a continuum of phosphorylated enzyme forms of decreasing activity. Phosphorylation of a single peptide, whether by the synthase kinase or the cyclic AMP dependent protein kinase, is critical for the associated kinetic changes during the initial phosphorylation. Conversely, dephosphorylation of this particular peptide is associated with complete activation. The protein phosphatase activity of the microsomal fraction may be separated into functionally and possibly also structurally different phosphorylase- and synthase-phosphatase activities, where the latter appears to be dependent on free cytoplasmic Ca2+. It is hypothesized that it is synthase-phosphatase activity that is absent in leukocytes from diabetic patients and is restored upon insulin treatment.

Topics: Diabetes Mellitus; Glycogen; Glycogen Synthase; Glycolysis; Humans; Insulin; Kinetics; Neutrophils; Phosphofructokinase-1; Reference Values

Topics: Blood Glucose; Diabetes Mellitus; Dietary Carbohydrates; Fatty Acids, Nonesterified; Glycogen; Humans; Hypoglycemia; Insulin; Muscles; Physical Exertion

Topics: Adolescent; Adult; Carboxylic Ester Hydrolases; Diabetes Mellitus; Glycogen; Humans; Lymphocytes; Male; Naphthol AS D Esterase; Naphthols; Periodic Acid-Schiff Reaction; T-Lymphocytes

Changes in hepatocyte glycogen morphology, liver glycogen, and blood glucose and insulin levels were studied at various time points after initiation of feeding in 10 week old genetic diabetic (db/db) mice (n = 8) and their lean littermates adapted to a controlled feeding regimen (6 h fed - 18 h fast). In spite of hyperinsulinemic (insulin greater than or equal to 97.60 +/- 88 uU/ml) and hyperglycemic (glucose greater than or equal to 437.1 +/- 49.5 mg/dl) conditions favoring glycogen synthesis, feeding-induced hepatic glycogen deposition was less efficient in the diabetic mice. An apparent decreased ability to mobilize hepatic glycogen during fasting and maintenance of relatively high fasting liver glycogen concentrations were however attributable to the anti-glycogenolytic effects of high blood glucose and insulin concentrations. Histochemical determinations (PAS) on livers of db/db mice showed typical lobular patterns of glycogen distribution during deposition and depletion of the polysaccharide. At stages of maximum glycogen (6 h after initiation of feeding), periportal cells displayed intensely stained masses of glycogen with centrilobular cells staining more diffusely. Ultrastructural studies revealed smooth endoplasmic reticulum (SER) in close association with glycogen during its deposition and depletion. The preservation of normal glycogen morphology and SER-glycogen ultrastructure indicates that functioning of the SER in hepatic glycogen metabolism is normal in midly diabetic (db/db) mice.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Endoplasmic Reticulum; Food; Glycogen; Histocytochemistry; Insulin; Liver; Male; Mice; Mice, Inbred Strains

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Blood Proteins; Diabetes Mellitus; Female; Glycogen; Humans; Leukocytes; Male; Middle Aged; Nucleic Acids; Phagocytosis

Topics: Acetylglucosaminidase; Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Diabetes Mellitus; Female; Glucuronidase; Glycogen; Histocytochemistry; Humans; Lipids; Male; Middle Aged; Neutrophils; Peroxidase

In a survey the effect of alcohol on carbohydrate tolerance and insulin is discussed. In an individually different degree alcohol, by hepatic, pancreatic and peripheral effects, contributes to manifestation of diabetes and negatively affects the secretion of insulin after manifestation of diabetes. In persons with intact metabolism the influence of alcohol partly results in an increase of stimulated insulin secretion. But from data found in literature must be assumed that a reduction of insulin secretion predominates in the long run. Moreover, diabetics run the risk of contracting hypoglycemia especially in cases where alcohol addicts are treated with hypoglycemizing drugs. Alcohol inhibits gluconeogenesis and glyconeogenesis and, at hepatic level, yet influences other enzyme systems. In addition we find in diabetes chronic liver lesions in a great number, quite independent of alcohol effects. However, dependent on a specific individual situation, alcohol may lead to severe metabolic disorders. In view of a general increase of alcohol addiction these aspects should result in a more critical dealing with alcohol problem in the general information of patients.

Topics: Diabetes Mellitus; Ethanol; Gluconeogenesis; Glucose Tolerance Test; Glycogen; Humans; Insulin; Insulin Secretion

Pancreatic ultrastructure as well as serum and pancreatic immunoreactive insulin content have been studied in nonoperated dogs rendered diabetic by the administration of growth hormone. In somatotrophic diabetes, the beta cells of the Langerhans islets were markedly degranulated and showed dilatation and prominence of the Golgi apparatus, cytoplasmic storage of glycogen, abnormalities of mitochondria as well as dilatation, vesiculation, degranulation and disruption of the endoplasmic reticulum. In some beta cells, damage was very severe and advanced. Accumulation of fat droplets and glycogen granules was found in the ductular epithelium. Fat droplets were also seen in the cytoplasm of a few alpha and acinar cells, however, these cells and the delta cells exhibited no major changes. In dogs with metasomatotrophic diabetes, neither regranulation nor neogenesis of beta cells were noted. Cytoplasmic glycogen storage was still apparent in both the beta and ductular epithelium cells. The serum insulin level was elevated in somatotrophic diabetes and reduced in metasomatotrophic diabetes; whereas, pancreatic immunoreactive insulin was decreased in somatotrophic diabetes and, to a greater extent, in metasomatotrophic diabetes. Present findings are consistent with the hypothesis that metasomatotrophic diabetes is a consequence of the overactivity, exhaustion and atrophy of the beta cells of the pancreatic islets produced by growth hormone.

Topics: Animals; Cytoplasmic Granules; Diabetes Mellitus; Dogs; Glycogen; Golgi Apparatus; Growth Hormone; Insulin; Islets of Langerhans; Male; Microscopy, Electron; Organoids; Pancreas

Topics: Body Weight; Diabetes Mellitus; Energy Metabolism; Glycogen; Humans; Male; Muscles; Oxygen Consumption; Physical Exertion

The metabolic changes in the heart--increased glycogen, triglycerides, and cyclic AMP, and decreased ATP and creatine phosphate--indicate that diabetes is a generalized disorder of cellular metabolism. The summarized observations provide additional biochemical reasons for early detection and treatment of patients with diabetes mellitus. Cognizance of three metabolic events are relevant to the treatment of the diabetic patient during acute cardiac events such as myocardial infarction.

Topics: Adenosine Triphosphate; Cardiovascular Diseases; Cyclic AMP; Diabetes Complications; Diabetes Mellitus; Glycogen; Humans; Myocardium; Phosphocreatine; Triglycerides

Muscle triglycerides and glycogen were measured in biopsy specimens of the vastus lateralis muscle before and after 1 h of ergometric exercise at 50 to 60% of maximal capacity (i. e. at a pulse rate during exercise of 180 minus age) in 3 groups of 19 to 35 year old, non-obese male subjects: 10 normals, 10 insulin dependent diabetic patients in relatively good control and 10 poorly controlled insulin dependent diabetic patients in whom insulin was withdrawn 24 h prior to examination. At rest in all subjects muscle triglyceride content was positively correlated with serum triglycerides(p < 0.001) and blood glucose (p < 0.05), resulting in elevated muscle triglyceride stores in the insulin deficient diabetic patients (17.9 +/- 1.8 mumol/g protein vs. 13.4 +/- 1.3 and 9.4 +/- 1.2 in the normal subjects and the well controlled diabetic patients; p < 0.05 and < 0.001). During exercise, utilisation of muscle triglycerides and glycogen were directly related to content at rest (p < 0.001), including the insulin-deprived patients with decreased glycogen. The decrease of muscle fat was associated with a rise in serum glycerol (p < 0.001) and non-esterified fatty acids (p < 0.001) during exercise.

Topics: Adult; Diabetes Mellitus; Glycogen; Humans; Insulin; Lipids; Male; Muscles; Physical Exertion; Triglycerides

The effect of diabetic metabolism on the human vascular wall studied, using the fetal cardiovascular system at birth as an experimental model. The ultrastructure of umbilical arteries from nine newborn children of nonsmoking diabetic mothers (White group D) was compared with that of 30 healthy nonsmokers. Intimal cushions, thickening of the basement membrane often with a multilaminal appearance, and glycogen accumulations, both in the cells of the intima and the media, were found. The cells of the intima were very rich in fibrillas, identical to the underlying media myocytes. Endothelial cell death with formation of a pseudoendothelium due to migrating myocytes might be the explanation.

Topics: Amniotic Fluid; Basement Membrane; Blood Glucose; Diabetes Mellitus; Female; Glycogen; Humans; Infant, Newborn; Smoking; Umbilical Arteries

The purpose of carbohydrate loading is to supersaturate with glycogen the muscles to be used in competition. The competition should be longer than 30 to 60 min. to fully utilize the glycogen stores. An exhausting exercise is first performed to deplete the glycogen stores, and a high-fat, high-protein diet is followed for three days to keep the glycogen stores low. After depletion of the muscles, a high-carbohydrate diet is followed for two to three days to restore and supersaturate the muscles with glycogen. The most important point to impress on the athlete is the nutritional adequacy of the entire diet. Though the technique of carbohydrate loading is a dietary manipulation emphasizing the intake of carbohydrate, the diet can be adequate with sound dietary planning.

Topics: Diabetes Mellitus; Diet; Dietary Carbohydrates; Energy Intake; Glycogen; Humans; Male; Muscles; Physical Education and Training; Sports Medicine; Triglycerides; Water

1. The effect of insulin (0.5, 10 and 50 munits/ml of perfusate) on glucose uptake and disposal in skeletal muscle was studied in the isolated perfused hindquarter of obese (fa/fa) and lean (Fa/Fa) Zucker rats and Osborne-Mendel rats. 2. A concentration of 0.5 munit of insulin/ml induced a significant increase in glucose uptake (approx. 2.5 mumol/min per 30 g of muscle) in lean Zucker rats and in Osborne-Mendel rats, and 10 munits of insulin/ml caused a further increase to approx. 6 mumol/min per 30 g of muscle; but 50 munits of insulin/ml had no additional stimulatory effect. In contrast, in obese Zucker rats only 10 and 50 munits of insulin/ml had a stimulatory effect on glucose uptake, the magnitude of which was decreased by 50-70% when compared with either lean control group. Since under no experimental condition tested was an accumulation of free glucose in muscle-cell water observed, the data suggest an impairment of insulin-stimulated glucose transport across the muscle-cell membrane in obese Zucker rats. 3. The intracellular disposal of glucose in skeletal muscle of obese Zucker rats was also insulin-insensitive: even at insulin concentrations that clearly stimulated glucose uptake, no effect of insulin on lactate oxidation (nor an inhibitory effect on alanine release) was observed; [14C]glucose incorporation into skeletal-muscle lipids was stimulated by 50 munits of insulin/ml, but the rate was still only 10% of that observed in lean Zucker rats. 4. The data indicate that the skeletal muscle of obese Zucker rats is insulin-resistant with respect to both glucose-transport mechanisms and intracellular pathways of glucose metabolism, such as lactate oxidation. The excessive degree of insulin-insensitivity in skeletal muscle of obese Zucker rats may represent a causal factor in the development of the glucose intolerance in this species.

Topics: Adipose Tissue; Animals; Body Composition; Diabetes Mellitus; Female; Glucose; Glycogen; In Vitro Techniques; Insulin; Insulin Resistance; Muscles; Obesity; Perfusion; Rats

Topics: Acetylcholine; Amino Acids; Animals; Cattle; Conjunctiva; Cornea; Corneal Diseases; Diabetes Mellitus; Epithelium; Glucose; Glycogen; Humans; Rabbits; Tears; Vitamin A Deficiency

Topics: Animals; Blood Glucose; Catecholamines; Diabetes Mellitus; Glycogen; Heart Rate; Humans; Insulin; Liver Glycogen; Muscles; Norepinephrine; Phentolamine; Physical Exertion; Posture; Propranolol; Rats

Topics: Diabetes Mellitus; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose; Glycogen; Homeostasis; Humans; Ketone Bodies; Muscles; Physical Exertion

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus; Glucose; Glycogen; Humans; Male; Muscles; Oxygen Consumption; Physical Exertion

Topics: Albuterol; Animals; Blood Glucose; Diabetes Mellitus; Ethanol; Glucagon; Gluconeogenesis; Glycogen; Humans; Hypoglycemia; Insulin; Liver; Liver Glycogen

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glycogen; Lactates; Liver; Male; Muscles; Physical Exertion; Rats; Streptozocin

Fenfluramine stimulates the glucose uptake of the isolated hemidiaphragm from normal and streptozotocin diabetic rats in the presence of insulin. The drug does not cause an increased storage of glycogen. During hind leg perfusion of the dog fenfluramine stimulated peripheral glucose uptake. No increase in lactate or in free fatty acids release was observed during prolonged infusions of the drug. Fenfluramine caused an improvement of glucose tolerance in normal glucose-primed rats. A single dose of fenfluramine significantly lowered the blood glucose levels in streptozotocin diabetic rats and in diabetic dogs treated with insulin. Prolonged treatment with fenfluramine of streptozotocin diabetic rats had no significant effect on blood glucose levels. Additional treatment for one week of insulin dependent diabetic dogs with small non-anorexic doses of fenfluramine resulted in slightly decreased blood glucose levels. The dogs could not be maintained on fenfluramine alone (without insulin).

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Drug Evaluation, Preclinical; Drug Synergism; Fatty Acids, Nonesterified; Fenfluramine; Glucose; Glucose Tolerance Test; Glycogen; Hindlimb; Insulin; Lactates; Male; Perfusion; Rats; Rats, Inbred Strains; Streptozocin; Time Factors

Topics: Animals; Diabetes Mellitus; Glycogen; Muscles; Physical Exertion; Rats; Streptozocin

Placentas of rats with diabetes mellitus induced by streptozotocin are investigated. Histologically, in the spongiosa zone we find dilated and congested maternal sinus as well as cysts of different size and number. These cysts contain granular eosinophilic material and cytotrophoblastic cells with large amount of glycogen. In our opinion, these cysts are large glycogen islets of the spongiosa zone respectively their remnants. However, similar findings we see in smaller extension in normal rat placentas too. The glycogen content in placentas of diabetic rats is in all localisations higher than in control cases. Comparable histological changes like in diabetic human placenta such as placental disturbances of maturation we don't find in the placental labyrinth of diabetic rats.

Topics: Animals; Diabetes Mellitus; Female; Glycogen; Placenta; Pregnancy; Pregnancy in Diabetics; Rats; Streptozocin

1. The specific radioactivities of glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, UDP-glucose and glycogen, derived from [14C]gluocose, were determined in the normal and insulin-deficient (streptozotocin-diabetic and anti-insulin-serum-treated) perfused non-working and working rat heart. 2. The specific radioactivities of all glucose metabolities reached a plateau after about 10 min, except that for glycogen, which increased slightly but steadily over the whole observation period of 30min. 3. The specific radio-activities of fructose 6-phosphate, UDP-glucose and glycogen were slignificantly lower in the streptozotocin-diabetic heart than in the normal heart. 4. Mechanical work in the normal rat heart increased the specific radioactivities of glucose 1-phosphate, UDP-glucose and glycogen, but had little or no effect on those of gluose 6-phosphate and fructose 6-phosphate. 5. In the normal heart insulin strongly increased the specific radioactivities of all gluocse metabolites under all conditions tested. The maximum values achieved in the normal working heart in the presence of insulin were only about 15-20% above those in the normal non-working heart in the presence of insulin for the phosphorylated intermediates and about 40% above for glycogen. 6. In the streptozotocin-diabetic heart, work restored the specific radioactivities of all glucose metabolities to about normal values. 7. In the streptozotocin-diabetic heart insulin strongly increased the specific radioactivities of the direct glycogen precursors glucose 1-phosphate and UDP-glucose; the effect of insulin on glucose 6-phosphate and fructose 6-phosphate was less marked. These results confirm previous findings that the primary metabolic lesion in diabetic heart muscle is a defect of glycogen synthesis. The specific radioactivity of glycogen itself was increased sixfold. 8. Under all conditions tested the specific radioactivity of glucose 1-phosphate was always found to be higher than that of glucose 6-phosphate. This indicated either compartmentation of a small but metabolically very active pool of glucose 6-phosphate, or the existence of a hitherto unknown pathway of metabolism in which glucose 1-phosphate is the primary reaction product. For a number of reasons the authors prefer the first explanation, which could also account for the observation that in the perfused normal working and non-working heart the specific radioactivity of fructose 6-phosphate was always found to be hi

Topics: Animals; Diabetes Mellitus; Glucose; Glycogen; Hexosephosphates; Immune Sera; In Vitro Techniques; Insulin; Insulin Antibodies; Male; Myocardial Contraction; Myocardium; Rats; Streptozocin; Uridine Diphosphate Glucose; Uridine Diphosphate Sugars

1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.

Topics: Adenylyl Cyclases; Adipose Tissue; Adrenal Cortex; Adrenocorticotropic Hormone; Animals; Cyclic AMP; Diabetes Mellitus; Dose-Response Relationship, Drug; Epinephrine; Glycogen; Glycogen Synthase; Insulin; Insulin Antibodies; Liver; Male; Muscles; Phosphorylases; Rats; Streptozocin; Theophylline

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dogs; Fatty Liver; Female; Glycogen; Humans; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Lipid Metabolism; Liver; Liver Cirrhosis; Liver Diseases; Male; Rabbits; Rats

Insulin is the key hormone of carbohydrate metabolism, it also influences the metabolism of fat and proteins. It lowers blood glucose by increasing glucose transport in muscle and adipose tissue and stimulates the synthesis of glycogen, fat, and protein. The anabolic action of insulin is antagonized by the catabolic action of glucagon. This hormone stimulates glycogenolysis and gluconeogenesis. The molar insulin: glucagon ratio is a parameter for an anabolic or a catabolic situation. Epinephrine also antagonizes insulin action. Like glucagon it stimulates glycogenolysis. In addition it reduces the insulin sensitivity of peripheral tissues and inhibits the release of insulin. Growth hormone decreases glucose uptake in muscle and adipose tissue gluconeogenesis in liver. In the presence of insulin, growth hormone stimulates protein synthesis. The net metabolic effects of a single hormone are directly related to the activity of other synergistic or antagonistic hormones.

Topics: Adipose Tissue; Amino Acids; Carbohydrate Metabolism; Carbohydrates; Diabetes Mellitus; Epinephrine; Glucagon; Glucose; Glycogen; Growth Hormone; Humans; Insulin; Lipid Metabolism; Liver; Muscles; Parenteral Nutrition; Proteins

Topics: Adult; Diabetes Mellitus; Ear, External; Female; Glycogen; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged

A study was made of insulin sensitivity of the adipose tissue biopsied in 11 healthy women, and in 10 women with normal weight suffering from newly-detected diabetes mellitus. In difference from healthy persons in the adipose tissue of patients suffering from diabetes, insulin in a concentration of 50 mu/ml failed to enhance the oxidation of glucose to CO2, and in a concentration of 50 and 100 mu/ml failed to enhance the glycogen synthesis from glucose. Reduction of the sensitivity of different ways of glucose metabolism in the adipose tissue to insulin in patients suffering from diabetes mellitus pointed to the possibility of disturbance of insulin interaction with the cell membrane in this disease.

Topics: Adipose Tissue; Adult; Diabetes Mellitus; Female; Glucose; Glycogen; Humans; In Vitro Techniques; Insulin; Middle Aged; Oxidation-Reduction

Quantitative glycogen determinations can be made in single blood and bone marrow cells, using microspectrophotometry or microfluorometry after staining with variants of the periodic acid--Schiff (PAS) reaction. These PAS variant reactions generally do not indicate the presence of non-glycogen PAS-positive substances, known to be prevalent in various hematopoietic cells, possibly due to masking of reactive groups. The specificity of the reaction in blood cells was ascertained by alpha-amylase digestion, which removed more than 95% of the PAS-positive material. Calibration of the PAS reaction was undertaken with a microdroplet model of pure leukocyte glycogen. The glycogen amounts in the droplets were determined by microinterferometry, the droplets were stained with a variant PAS reaction, and the total extinction of the reaction product in the stained droplets was determined by microspectrophotometry. The extinction coefficient (k) was obtained from the equation k equals Etot divided by M where (Etot) is the total extinction as determined by microspectrophotometry and (M) the dry glycogen amount as determined by microinterferometry. The microinterferometric dry mass determinations were calibrated by X-ray absorption in order to obtain the absolute amounts of glycogen. For practical purposes a reference system was made of normal neutrophil leukocytes. The glycogen content in the reference neutrophils was first determined with the micromodel. These neutrophils, now with a known glycogen amount, were stained with the PAS reagents and measured microspectrophotometrically in parallel with cells containing an unknown glycogen amount. Alternatively, the staining was made with a fluorescent PAS reaction, and the glycogen content determined by microfluorometry. Both methods appeared suitable for determining the glycogen content of blood cells from patients with various diseases, though the microfluorometric method was preferable for measurements of small amounts of inhomogeneously distributed glycogen. The mean glycogen content of normal neutrophil leukocytes was found to be 13.6 times 10(-12) g. The content was increased in infectious diseases such as pneumonia and tonisillitis, as well as in polycythemia vera and myelofibrosis, while low amounts were found in untreated chronic myelocytic leukemia. In chronic myelocytic leukemia in remission, the glycogen content of mature neutrophils had completely normalized. Erythroblasts normally do not contain detectable amou

Topics: Autoradiography; Blood Cells; Bone Marrow; Bone Marrow Cells; Communicable Diseases; Diabetes Mellitus; Fluorometry; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Interferometry; Leukemia; Microradiography; Models, Biological; Myocardial Infarction; Neutrophils; Periodic Acid-Schiff Reaction; Polycythemia; Spectrophotometry; Thalassemia; X-Rays

Topics: Blood Bactericidal Activity; Blood Glucose; Chemotaxis, Leukocyte; Diabetes Mellitus; Glycogen; Glycolysis; Humans; Insulin; Leukocytes; Phagocytosis

Two concepts are advanced to explain some fo the puzzling biochemical features found in nonketotic hyperosmolar diabetic coma. It is firstly suggested that an insulinised liver (reflecting residual beta-cell secretory activity) coexists with a diabetic periphery, thereby inactivating intrahepatic oxidation of incoming free fatty acids, which are directed largly along nonketogenic metabolic pathways such as triglyceride synthesis. This could account for the lack of hyperketonaemia. Secondly, it is hypothesised that within the liver enhanced neoglucogenesis occurs, due to the prevailing portal-vein into ratio of glucagon to insulin, and is mainly responsible for the development of massive hyperglycaemia.

Topics: Animals; Diabetes Mellitus; Diabetic Coma; Fatty Acids, Nonesterified; Glucagon; Glycogen; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Liver; Metabolic Clearance Rate; Osmolar Concentration; Oxidation-Reduction; Rats; Triglycerides

In diabetes mellitus abnormal quantiites of glycoprotein may be formed in the basement membrane of the glomerulus and both renal function and size may increase. It is suggested that these changes, of quite different potential significance, have a common origin an increased rate of uridine-triphosphate synthesis resulting from hyperglycemia.

Topics: Animals; Basement Membrane; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glycogen; Glycoproteins; Humans; Hyperglycemia; Hypertrophy; Kidney; Kidney Diseases; Kidney Glomerulus; Rats; RNA; Sclerosis; Uracil Nucleotides

Testosterone affects glycogen levels in perineal and skeletal muscles by two distinct mechanisms. Both of them show similar sensitivity to androgens (0.1 mg/rat/day of testosterone being effective) and to antiandrogen administration. However, they differ because of the pattern of glycogen increase (early after the androgen injection in the perineal muscles; slowly and with a linear function of time in the skeletal muscles), and because of the different sensitivities to adrenolectomy, diabetes and hypophysectomy. Also, the biochemical changes induced by testosterone in muscles differ. The rate of sugar uptake and phosphorylation is increased in the perineal muscle only; the rate of glucose incorporation into glycogen is increased in the perineal but depressed in the skeletal muscles. Therefore, in the former case glycogen accumulation depends mainly on increased synthesis; in the latter, it is probably the result of a glycogen sparing effect.

Topics: Adrenalectomy; Animals; Carbon Radioisotopes; Castration; Deoxyglucose; Diabetes Mellitus; Glucose; Glycogen; Glycogen Synthase; Hydrocortisone; Hypophysectomy; Insulin; Male; Muscles; Rats; Stimulation, Chemical; Streptozocin; Testosterone; Xylose

Investigations on carbonhydrates were carried out with special regard to acid mucopolysaccharides and glycogen. The fluorescence-microscopical proof of acid micropolysaccharides with acridinorange (pH=3,3) and by means of the pseudoisocyanin-reaction (proof of-SO3H-groups) gave positive results on elastic membranes of blood vessels. These results were correlating to the increase of the diabetes mellitus. Healthy Wistar-rats did not show metachromasia with toluidinblue in the walls of the blood vessels, whereas in streptozotocin-diabetes there was strong metachromasia shown by these structures. The stages of diabetes in man were also correlated to an increase of metachromasia. The PAS-reaction, the staining with Best's carmine and the reaction with alizarinblue S for the proof of glycogen were positive in all blood vessels investigated.

Topics: Animals; Arteries; Carbohydrates; Diabetes Mellitus; Diabetic Angiopathies; Elastic Tissue; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Rats; Streptozocin

The glucose utilization by different skeletal muscle tissues of short-term streptozotocin treated Wistar rats was studied both in vivo and in vitro. The findings permit the following statements: The reduced metabolic conversion of glucose is mainly the result of the diminished transport of glucose into the muscle cells. The utilization of the glucose taken up by the muscle cells for synthesis of glycogen is unchanged in the diabetic animals and can be stimulated by insulin correspondingly as in normal rats. The conversion of the glucose metabolized by the cells to lactate and the time course of the specific activity of glycogen and lactate lead to the conclusion that glycogenolysis in the muscles of streptozotocin diabetic rats during the incubation is enhanced.

Topics: Animals; Diabetes Mellitus; Glucose; Glycogen; Lactates; Male; Muscles; Myofibrils; Rats; Streptozocin

The effect of clofibrate (CPIB) on lipid metabolism was studied in male rats rendered diabetic by intravenous injection of 80 mg/kg of streptozotocin. After 1 wk, the rats received by gastric intubation 242 mg/kg/day of CPIB for 7 days. Liver lipid concentration remained unchanged in experimental diabetes and after treatment with CPIB; however, due to decreased liver weight, total liver lipids were lower in diabetic rats. Elevation of cholesterol, phospholipids, and triglycerides in the serum of diabetic rats was reversed by CPIB treatment. Hepatic cholesterol synthesis in diabetic rats was suppressed to approximately 1/10 of that in normal rats. Treatment with CPIB abolished this residual cholesterogenic activity. Diabetes had no effect on intestinal cholesterol synthesis; a slight increase was noted after CPIB treatment. Basal and norepinephrine-induced lipolysis in fat pads was elevated in diabetic rats; CPIB had no effect on these changes. The data show that the elevated serum lipids in diabetic rats are lowered by treatment with C-IB. It was concluded that the hypocholesterolemic activity of clofibrate in rats is not caused by its suppression of hepatic cholesterol synthesis.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Clofibrate; Diabetes Mellitus; Eating; Fatty Acids, Nonesterified; Glycogen; Intestinal Mucosa; Lipid Metabolism; Lipoproteins, HDL; Liver; Male; Phospholipids; Rats; Streptozocin; Triglycerides

Topics: Blood Glucose; Brain; Carbohydrate Metabolism; Diabetes Mellitus; Diet; Dietary Carbohydrates; Glucokinase; Glucose; Glucosephosphate Dehydrogenase; Glycogen; Glycogen Synthase; Glycolysis; Humans; Ketone Bodies; Liver; Liver Glycogen; Muscles; Physical Exertion

Alloxan-induced diabetes of 4 days duration produced metabolite changes in brain compatible with severe reduction in cerebral metabolism (phosphocreatine increased 70%), and reduced phosphofructokinase activity (fructose diphosphate levels fell 38%). There was a 56% reduction in brain lactate concentration, but pyruvate levels were unchanged. In 5 of 23 animals, brain glycogen levels increased; in the remainder blycogen levels decreased. Brain fructose concentration, 0.4 mmol/kg, was only 1/30 of the glucose concentration. The alloxan-treated animals were also severely dehydrated. Therefore, to determine the casual relation of insulin deficiency to these findings, the effects of chronic dehydration and acute insulin deficiency were investigated. Findings in the brains of severely dehydrated animals (water deprivation and mannitol injections for 4 days) were almost identical with those seen after alloxan treatment. The exceptions were that, in the dehydrated mice, reductions in lactate and pyruvate were proportional, and glycogen levels were consistently reduced. In acute diabetes (6 to 24 hours after repeated anti-insulin serum injections) P-creatine, fructose diphosphate, and lactate levels were normal. Pyruvate levels were normal at 6 hours, but increased 39% by 12 to 24 hours; glycogen was 36% higher at 6 hours and 63% at 12 to 24 hours. Insulin (and glucose) appeared to be specific in correcting the metabolic abnormalities found in the brains of animals with alloxan-induced diabetes. At 4 and one half hours after treatment with insulin and glucose, glucose 6-phosphate levels fell 25%, fructose diphosphate increased 28%, and lactate and the lactate to pyruvate ratio returned to normal; glycogen increased 50%. However, the treatment also had a dramatic clinical effect. Since animals gained 8 to 27% of body weight during therapy, at least some of the improvements in metabolite levels could be related to rehydration.

Topics: Animals; Blood Glucose; Brain; Carbohydrate Metabolism; Dehydration; Diabetes Mellitus; Diabetes Mellitus, Experimental; Energy Metabolism; Glycogen; Hydroxybutyrates; Immune Sera; Insulin; Insulin Antibodies; Mannitol; Mice

In an electron-microscopic study of the skin of a patient with scleredema adultorum (Buschke) and diabetes mellitus, the unmyelinated nerve fibres showed accumulations of glycogen. On morphological grounds, these accumulations appeared to be located in the axons.

Topics: Axons; Diabetes Complications; Diabetes Mellitus; Female; Glycogen; Humans; Middle Aged; Peripheral Nerves; Scleredema Adultorum; Skin

Topics: Adult; Biopsy; Blood Glucose; Diabetes Mellitus; Ear, External; Glycogen; Humans; Middle Aged; Periodic Acid; Prediabetic State; Skin; Staining and Labeling

Topics: Adult; Blood Cell Count; Blood Glucose; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Glucosephosphate Dehydrogenase; Glucosephosphates; Glycogen; Humans; Lymphocytes; Middle Aged; Periodic Acid; Phosphogluconate Dehydrogenase; Staining and Labeling

Topics: Adenylyl Cyclases; Binding Sites; Diabetes Mellitus; Fasting; Fatty Acids, Nonesterified; Genotype; Glycogen; Glycogen Storage Disease; Humans; Insulin; Ketone Bodies; Phenotype; Prediabetic State

Topics: Blood Platelets; Carbon Radioisotopes; Cyclopentanes; Diabetes Mellitus; Enzyme Repression; Glycogen; Glycogen Synthase; Humans; Hypoglycemic Agents; In Vitro Techniques; Pyrroles; Sulfonylurea Compounds

Topics: Animals; Cricetinae; Diabetes Mellitus; Diabetic Ketoacidosis; Diabetic Nephropathies; Diabetic Retinopathy; Disease Models, Animal; Female; Glucose; Glycogen; Glycosuria; Histocytochemistry; Islets of Langerhans; Kidney; Male; Retina

Topics: Acid-Base Equilibrium; Animals; Carbon Dioxide; Carbon Radioisotopes; Diabetes Mellitus; Diabetes Mellitus, Experimental; Gluconeogenesis; Glycogen; Glycolysis; Hydrogen-Ion Concentration; In Vitro Techniques; Insulin; Kidney Cortex; Lactates; Liver Glycogen; Male; Muscles; Rats; Streptozocin

Topics: Animals; Cell Movement; Diabetes Mellitus; Epithelial Cells; Epithelium; Female; Glycogen; Hyperglycemia; Insulin; Male; Mouth Mucosa; Rats; Streptozocin; Wound Healing

Topics: Animals; Diabetes Mellitus; Dietary Carbohydrates; Fasting; Glucose; Glucosephosphate Dehydrogenase; Glycogen; Hexokinase; Intestinal Mucosa; Jejunum; Kidney; Liver Glycogen; Male; Microscopy, Electron; Pyruvate Kinase; Rats; Streptozocin

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glycogen; Histocytochemistry; Microscopy, Electron; Neuroglia; Neurons; Rats; Retina; Streptozocin

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O(2) consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood-brain barrier

Topics: Acetoacetates; Acetyl Coenzyme A; Adenine Nucleotides; Animals; Biological Transport; Blood Glucose; Blood-Brain Barrier; Brain; Citrates; Diabetes Mellitus; Female; Glucose; Glycogen; Hydroxybutyrates; Ketone Bodies; Lactates; Pentobarbital; Phlorhizin; Phosphocreatine; Rats; Spectrometry, Fluorescence; Starvation; Streptozocin; Time Factors

Male rats rendered diabetic by the intravenous injection of streptozotocin (150mg/kg) were treated with a long-acting insulin for 1 week, then allowed to develop ketoacidosis. By using sampling techniques designed to avoid the use of anaesthesia and extended anoxic periods, sequential measurements of metabolic intermediates were made in blood, liver, cerebrospinal fluid and brain at 24h intervals after the last insulin injection. Measurements in blood and liver suggested a rapid increase in hepatic glycogenolysis and gluconeogenesis and peripheral-depot lipolysis between 24 and 48h after the last insulin injection, whereas blood and liver ketone-body and triglyceride concentrations rose more slowly. The changing metabolic patterns occurring with increasing time of insulin deprivation stress the importance of sequential compared with static measurements in experimental diabetes. Data are presented for brain metabolic intermediates in diabetic ketoacidosis, and support recent evidence that glucose plays a less important role in brain oxidative metabolism in ketotic states.

Topics: Animals; Antibodies; Blood Glucose; Body Weight; Brain; Diabetes Mellitus; Diabetic Ketoacidosis; Gluconeogenesis; Glycogen; Insulin; Ketone Bodies; Lipid Mobilization; Liver; Male; Organ Size; Radioimmunoassay; Rats; Streptozocin; Time Factors; Triglycerides

Topics: Adenosine Triphosphate; Animals; Blood Platelets; Diabetes Mellitus; Ethanol; Fluorometry; Glycogen; Glycolysis; Male; Platelet Adhesiveness; Rats; Rutin; Streptozocin

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetic Ketoacidosis; Fatty Acids, Nonesterified; Glucose; Glycerol; Glycogen; Insulin; Ketone Bodies; Lactates; Liver; Male; Physical Exertion; Rats; Streptozocin

Topics: Adrenal Medulla; Adrenalectomy; Animals; Blood Glucose; Diabetes Mellitus; Enzyme Activation; Epinephrine; Glycogen; Guinea Pigs; Injections, Subcutaneous; Insulin Antagonists; Insulin Antibodies; Lactates; Male; Muscle Proteins; Muscles; Phosphorylase Kinase; Phosphorylases; Rats; Streptozocin

Topics: Acetoacetates; Animals; Blood Glucose; Caprylates; Cattle; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glucose; Glucose Tolerance Test; Glycogen; Glycolysis; Insulin; Ketone Bodies; Muscles; Oleic Acids; Oxidation-Reduction; Perfusion; Pyruvates; Rats; Rest; Starvation; Streptozocin; Swine

Topics: Aged; Animals; Cataract; Cytoplasmic Granules; Diabetes Complications; Diabetes Mellitus; Glycogen; Humans; Lens, Crystalline; Rats; Streptozocin

Topics: Animals; Castration; Diabetes Mellitus; Drug Synergism; Glycogen; Glycogen Synthase; Insulin; Male; Muscles; Perineum; Rats; Streptozocin; Testosterone; Time Factors

Topics: Adenylyl Cyclases; Animals; Biological Transport; Calcium; Chromatography, Ion Exchange; Chromatography, Paper; Diabetes Mellitus; Glucosephosphates; Glycogen; Glycogen Synthase; Male; Microscopy, Electron; Muscles; Phosphoric Diester Hydrolases; Phosphorus Radioisotopes; Streptozocin; Subcellular Fractions; Time Factors; Tritium; Ultracentrifugation

A combined ultrastructural and functional approach was employed to define the effects of duration of diabetes and of diet on various aspects of lipid metabolism in rats with severe streptozotocin (SZ)-induced insulin deficiency. Plasma triglyceride (TG) levels rose to a mean of 479 mg/100 ml 24 h after SZ administration in rats eating a fat-free, high carbohydrate diet as compared to a mean of 324 mg/100 ml in rats eating a high fat diet. These changes were associated with a commensurate increase in hepatocyte Golgi very low density lipoprotein (VLDL) content, but only a small increase in estimates of VLDL-TG secretion rate (post-Triton WR 1339 increment in plasma TG level). Although these findings are consistent with the thesis that VLDL-TG synthesis and secretion are increased 24 h after administration of SZ, it seemed unlikely that the observed increase in VLDL-TG secretion could entirely account for the severity of the hypertriglyceridemia. Thus, although lipoprotein removal rate was not measured directly, it was necessary to postulate that a defect in VLDL-TG removal was also present at this stage. Hypertriglyceridemia was still present 7 days later, only in this instance plasma TG levels were higher in rats eating the high fat diet (a mean of 589 mg/100 ml, as compared to 263 mg/100 ml). Rats with diabetes of 7-day duration had a 50% decrease in both TG entry rate and hepatocyte Golgi complex VLDL content, irrespective of diet. Thus, there was no evidence of increased VLDL-TG secretion in chronic insulin deficiency. In this instance, although not assessed directly, it was necessary to postulate that the hypertriglyceridemia in chronically insulin-deficient rats is due entirely to a defect in lipoprotein removal, involving both dietary and endogenous fat.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Diet; Dietary Carbohydrates; Fatty Acids, Nonesterified; Female; Glycogen; Golgi Apparatus; Insulin; Lipoproteins, VLDL; Liver; Microscopy, Electron; Rats; Streptozocin; Time Factors; Triglycerides

Topics: Diabetes Mellitus; Diabetic Nephropathies; Glycogen; Humans; Kidney; Kidney Papillary Necrosis; Kidney Tubules; Syndrome

Topics: Adult; Aged; Diabetes Mellitus; Glycogen; Humans; Leukocytes; Middle Aged; Neutrophils

Topics: Animals; Blood Glucose; Diabetes Mellitus; Female; Glucose; Glycogen; Insulin; Islets of Langerhans; Kidney; Liver; Masticatory Muscles; Mice; Mice, Inbred C57BL; Mucous Membrane; Palate; Periodontitis; Periodontium; Rodent Diseases

Topics: Basement Membrane; Capillaries; Cytoplasm; Diabetes Mellitus; Diabetic Angiopathies; Glycogen; Histocytochemistry; Humans; Lymphocytes; Staining and Labeling

Topics: Animals; Diabetes Mellitus; Enzyme Activation; Glucose; Glucosyltransferases; Glycogen; Glycogen Synthase; Heart; Hexokinase; Insulin; Isoenzymes; Male; Metabolic Diseases; Myocardium; Perfusion; Phosphates; Rats; Streptozocin

In the absence of glucose, insulin stimulated the incorporation of (14)C-labelled amino acids into protein by perfused rat hearts that had been previously substantially depleted of endogenous glucose, glucose 6-phosphate and glycogen by substrate-free perfusion. This stimulation was also demonstrated in hearts perfused with buffer containing 2-deoxy-d-glucose, an inhibitor of glucose utilization. It is concluded that insulin exerts an effect on protein synthesis independent of its action on glucose metabolism. Streptozotocin-induced diabetes was found to have no effect either on (14)C-labelled amino acid incorporation by the perfused heart or on the polyribosome profile and amino acid-incorporating activity of polyribosomes prepared from the non-perfused hearts of these insulin-deficient rats, which show marked abnormalities in glucose metabolism. Protein synthesis was not diminished in the perfused hearts from rats treated with anti-insulin antiserum. The significance of these findings is discussed in relation to the reported effects of insulin deficiency on protein synthesis in skeletal muscle.

Topics: Animals; Blood Glucose; Carbon Isotopes; Centrifugation, Density Gradient; Diabetes Mellitus; Glucose; Glucosephosphates; Glycogen; Guinea Pigs; Heart; Immune Sera; Insulin; Insulin Antibodies; Kinetics; Male; Muscle Proteins; Myocardium; Perfusion; Polyribosomes; Rats; Streptozocin

Topics: Animals; Blood Glucose; Carbon Isotopes; Diabetes Mellitus; Glucose; Glucosephosphates; Glycogen; Glycogen Synthase; Heart; Hexokinase; Insulin; Kinetics; Male; Myocardium; Phosphoric Monoester Hydrolases; Phosphorylases; Rats; Streptozocin; Uridine Diphosphate Sugars

Topics: Adult; Amylases; Atrophy; Biopsy; Buffers; Cytoplasmic Granules; Diabetes Mellitus; Epithelial Cells; Epithelium; Female; Glycogen; Humans; Iris; Male; Methods; Microscopy, Electron; Middle Aged; Pigments, Biological; Ribonucleases; Time Factors

Topics: Adenylyl Cyclases; Adipose Tissue; Animals; Blood Glucose; Cardiovascular System; Cats; Cyclic AMP; Diabetes Mellitus; Digestive System; Dogs; Glucagon; Gluconeogenesis; Glycogen; Hormones; Humans; Lipid Metabolism; Liver; Muscles; Pancreas; Proteins; Rabbits; Rats; Water-Electrolyte Balance

Topics: Acute Disease; Animals; Cytoplasm; Cytoplasmic Granules; Diabetes Mellitus; Disease Models, Animal; Endoplasmic Reticulum; Glycogen; Guinea Pigs; Islets of Langerhans; Microscopy; Microscopy, Electron

Topics: Adult; Aged; Aging; Cataract; Cytoplasm; Diabetes Mellitus; Epithelium; Female; Glaucoma; Glycogen; Humans; Hypertension; Iris; Male; Melanins; Microscopy, Electron; Middle Aged; Pigments, Biological

Topics: Aging; Basement Membrane; Capillaries; Diabetes Mellitus; Endothelium; Glycogen; Histocytochemistry; Humans; Iris; Microscopy, Electron; Muscle, Smooth; Organoids; Pupil

Topics: Adult; Diabetes Mellitus; Ear, External; Female; Glycogen; Humans; Male; Prediabetic State; Sebaceous Glands

Topics: Animals; Antibiotics, Antineoplastic; Carbon Isotopes; Diabetes Mellitus; Glucose; Glucosyltransferases; Glycogen; Glycogen Synthase; Hexokinase; Myocardium; Rats; Streptozocin

Topics: Alanine; Animals; Blood Glucose; Brain Chemistry; Diabetes Mellitus; Gluconeogenesis; Glutamates; Glycine; Glycogen; Hyperglycemia; Injections, Intravenous; Ketones; Male; Rats; Starvation; Streptozocin

1. The activities of gluconeogenic and glycolytic enzymes and the concentrations of citrate, ammonia, amino acids, glycogen, glucose 6-phosphate, acetyl-CoA, lactate and pyruvate were measured in kidney cortex of normal, diabetic, cortisone-treated and growth hormone-treated rats. 2. In kidney cortex of diabetic, cortisone-treated and growth hormone-treated rats the activities of glucose 6-phosphatase (EC 3.1.3.9), fructose 1,6-diphosphatase (EC 3.1.3.11) and phosphopyruvate carboxylase (EC 4.1.1.32) were increased. 3. The activities of glutamate dehydrogenase (EC 1.4.1.3), alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.10) and pyruvate carboxylase (EC 6.4.1.1) were increased in diabetic and cortisone-treated rats. In growth hormone-treated rats the activity of aspartate aminotransferase was depressed but those of the other three enzymes were unchanged. 4. The activity of hexokinase (EC 2.7.1.1) was not altered in any of these conditions. Phosphofructokinase (EC 2.7.1.11) activity was depressed only in growth hormone-treated rats. Pyruvate kinase (EC 2.7.1.40) activity was depressed in cortisone-treated and growth hormone-treated rats but unchanged in diabetic rats. 5. Amino acids, acetyl-CoA and glucose 6-phosphate contents were increased in rat kidneys in all these three conditions. Ammonia content was increased in diabetic and cortisone-treated rats but was markedly diminished in growth hormone-treated rats. 6. The [lactate]/[pyruvate] ratio was elevated in diabetic and cortisone-treated rats but unchanged in growth hormone-treated rats. Citrate content was increased in the kidney cortex of diabetic and growth hormone-treated rats but was unchanged in cortisone-treated rats. The activity of ATP citrate lyase (EC 4.1.3.8) was depressed in diabetic and growth hormone-treated rats but was increased in cortisone-treated rats. 7. Glycogen content was moderately elevated in growth hormone-treated rats and markedly elevated in diabetic rats, whereas no change in glycogen content was observed in cortisone-treated rats. Glycogen synthetase (EC 2.4.1.11) activity was unchanged in all these three conditions. Phosphorylase (EC 2.4.1.1) activity was not affected in cortisone-treated rats but was depressed in diabetic and growth hormone-treated rats.

Topics: Alanine Transaminase; Amino Acids; Animals; Aspartate Aminotransferases; Carboxy-Lyases; Citrates; Coenzyme A; Cortisone; Diabetes Mellitus; Fructose-Bisphosphatase; Glucose; Glucose-6-Phosphatase; Glutamate Dehydrogenase; Glycogen; Growth Hormone; Hexokinase; Kidney; Kidney Cortex; Ligases; Male; Phosphofructokinase-1; Pyruvate Kinase; Rats

Topics: Blood Glucose; Diabetes Mellitus; Fructose; Glucose; Glycogen; Humans; Lactates; Liver Glycogen; Muscles; Stimulation, Chemical

Topics: Animals; Blood Glucose; Cell Nucleus; Cricetinae; Cytoplasm; Diabetes Mellitus; Disease Models, Animal; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Microscopy, Electron; Mitochondria

Topics: Animals; Cytoplasm; Diabetes Mellitus; Endoplasmic Reticulum; Epithelial Cells; Epithelium; Glycogen; Golgi Apparatus; Guinea Pigs; Insulin Antibodies; Islets of Langerhans; Lysosomes; Microscopy, Electron; Monocytes

Topics: Blood Platelets; Diabetes Mellitus; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Liver Cirrhosis; Microscopy, Phase-Contrast; Myeloproliferative Disorders; Polycythemia; Primary Myelofibrosis; Purpura, Thrombocytopenic; Remission, Spontaneous; Uremia; von Willebrand Diseases

Topics: Adipose Tissue; Age Factors; Animals; Biological Assay; Carbon Isotopes; Diabetes Mellitus; Diabetic Ketoacidosis; Diaphragm; Epididymis; Glycogen; Humans; Insulin; Male; Methods; Rats

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Glucose; Glucosyltransferases; Glycogen; Glycogen Synthase; Humans; Insulin; Male; Middle Aged; Muscles; Physical Exertion; Time Factors

The site(s) of action of a bovine pituitary diabetogenic peptide that produces hyperglycemia and hyperinsulinemia in vivo (dogs or humans) was investigated in vitro. When rat diaphragms were incubated with the peptide in the presence of insulin, the peptide depressed insulin-mediated (a) glucose uptake, (b) glycogen synthesis, and (c) glycogen synthase activation (conversion of D to I form). Incubation with the peptide alone resulted in small increases in (a), (b), and (c). Insulin-mediated glycogen synthase kinase inactivation was inhibited when both insulin and peptide were present (d), whereas glycogen synthase kinase activity was lowered by the peptide alone. High doses of insulin completely reversed inhibitory effects of the peptide on glycogen synthesis. Therefore, the hyperglycemic and anti-insulin properties of this peptide in vivo can possibly be explained by the partial blocking action of the peptide on insulin-mediated glucose uptake and glycogenesis.

Topics: Animals; Binding Sites; Carbon Isotopes; Depression, Chemical; Diabetes Mellitus; Diaphragm; Enzyme Activation; Glucose; Glycogen; Glycogen Synthase; In Vitro Techniques; Insulin; Insulin Antagonists; Male; Peptides; Phosphotransferases; Pituitary Gland; Rats

Topics: Adult; Biguanides; Blood Glucose; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diet, Diabetic; Female; Glucosyltransferases; Glycogen; Glycogen Synthase; Glycosuria; Humans; Insulin; Male; Methods; Middle Aged; Muscles; Physical Exertion; Sulfonylurea Compounds; Time Factors

Topics: Cell Nucleus; Child; Cytoplasm; Diabetes Mellitus; Gluconeogenesis; Glycogen; Glycosuria; Humans; Liver; Liver Diseases; Microscopy; Prediabetic State; Time Factors

Topics: Animals; Buffers; Centrifugation; Centrifugation, Density Gradient; Chloroform; Cricetinae; Diabetes Mellitus; Glycine; Glycogen; Liver

Topics: Animals; Biguanides; Butanes; Carbon Dioxide; Carbon Isotopes; Diabetes Mellitus; Diaphragm; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose; Glycogen; Guinea Pigs; Hexokinase; Insulin; Lactates; Liver; Metformin; Muscles; Phenformin; Pyruvates; Rats

Topics: Alcoholism; Animals; Bile Ducts, Intrahepatic; Diabetes Mellitus; Glycogen; Golgi Apparatus; Hemochromatosis; Humans; Liver; Lysosomes; Microscopy, Electron; Mitochondria, Liver; Rats

Topics: Adolescent; Adult; Aged; Child; Diabetes Mellitus; Diet, Diabetic; Dietary Carbohydrates; Glucosyltransferases; Glycogen; Humans; Insulin; Middle Aged; Muscles; Physical Exertion; Time Factors

Topics: Adipose Tissue; Adult; Aged; Diabetes Complications; Diabetes Mellitus; Female; Glycogen; Humans; Male; Middle Aged; Muscles; Surgical Procedures, Operative; Water

Topics: Azides; Blood Platelets; Diabetes Mellitus; Epinephrine; Fluorides; Glycogen; Humans

Topics: Amino Sugars; Animals; Anti-Bacterial Agents; Carbon Dioxide; Carbon Isotopes; Diabetes Mellitus; Fasting; Fructose; Glucose; Glycogen; Glycosuria; Hydrazones; Insulin; Lipids; Male; Nitroso Compounds; Oxidation-Reduction; Rats; Sorbitol; Streptozocin; Xylitol

Topics: Child; Diabetes Mellitus; Glycogen; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Pancreas

Topics: Amino Acids; Diabetes Mellitus; Diabetic Ketoacidosis; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Humans; Insulin

Topics: Animals; Anti-Bacterial Agents; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Experimental; Female; Fetus; Glycogen; Placenta; Pregnancy; Pregnancy in Diabetics; Rats

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Glucagon; Glycogen; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Time Factors

1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (;working heart'). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [(14)C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and (14)CO(2)). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue contents of hexose phosphates and of citrate. There were similar findings when working hearts from streptozotocin-diabetic rats with insulin added to the medium were compared with normal hearts. 8. The effects of insulin addition or of the chronic diabetic state could be explained in terms of an action of insulin on glucose transport. Increased heart work also acted at this site, but in addition there was evidence for altered regulation of glycolysis mediated by changes in tissue contents of aden

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Antibiotics, Antineoplastic; Biomechanical Phenomena; Carbon Isotopes; Citrates; Diabetes Mellitus; Diabetes Mellitus, Experimental; Epinephrine; Glucose; Glycogen; Glycolysis; Heart; Hexosephosphates; Insulin; Muscle Contraction; Myocardium; Oxygen Consumption; Perfusion; Phosphocreatine; Rats; Time Factors

Topics: Blood Cell Count; Carbohydrate Metabolism; Diabetes Mellitus; Diabetic Angiopathies; Female; Glycogen; Histocytochemistry; Humans; Lymphocytes; Methods

1. The metabolism of [U-(14)C]glucose in perfused resting and contracting diaphragm muscle from normal rats and rats made diabetic with streptozotocin was studied in the presence and absence of insulin. 2. The incorporation of [U-(14)C]-glucose into glycogen and oligosaccharides was stimulated by insulin under all experimental conditions studied. 3. In the normal perfused resting diaphragm muscle the incorporation of radioactivity from [(14)C]glucose into lactate and CO(2) was not affected by insulin. 4. Periodic contractions, induced by electrical stimulation of the perfused diaphragm muscle in the absence of insulin, caused an increased incorporation of (14)C into glycogen and hexose phosphate esters, whereas incorporation of (14)C into lactate was greatly decreased. Production of (14)CO(2) in the contracting muscle was not significantly different from that in resting muscle. Addition of insulin to the perfusion liquid caused a further increase in formation of [(14)C]-glycogen in contracting muscle to values reached in the resting muscle in the presence of insulin. Formation of [(14)C]lactate was also stimulated by insulin, to values close to those found in the resting muscle in the presence of insulin. 5. In the diabetic resting muscle the rate of glucose metabolism was very low in the absence of insulin. Insulin increased formation of [(14)C]glycogen to the value found in normal muscle in the absence of insulin. Production of (14)CO(2) and formation of [(14)C]hexose phosphate remained unchanged. 6. In the diabetic contracting muscle production of (14)CO(2) was increased to values approaching those found in normal contracting muscle. Formation of [(14)C]lactate and [(14)C]glycogen was also increased by contraction, to normal values. Only traces of [(14)C]hexose phosphate were detectable. Addition of insulin to the perfusion medium stimulated formation of [(14)C]glycogen, to values found in normal contracting muscle. Production of [(14)C]hexose phosphate was stimulated by insulin, to approximately the values found in the normal contracting muscle. Production of (14)CO(2) and [(14)C]lactate, however, was not significantly affected by insulin. 7. These results indicate that the defects of glucose metabolism observed in perfused resting diabetic diaphragm muscle can be partially corrected by contraction, and in the presence of insulin the contracting diabetic muscle has a completely normal pattern of glycogen synthesis and lactate production, but CO(2) pro

Topics: Animals; Antibiotics, Antineoplastic; Carbon Dioxide; Carbon Isotopes; Chromatography, Paper; Diabetes Mellitus; Diaphragm; Electric Stimulation; Glucose; Glycogen; Hexosephosphates; In Vitro Techniques; Insulin; Lactates; Muscle Contraction; Oligosaccharides; Perfusion; Rats

Topics: Aged; Blood Glucose; Blood Pressure; Blood Vessels; Cataract; Diabetes Complications; Diabetes Mellitus; Female; Glycogen; Humans; Iris; Male; Microscopy, Electron; Middle Aged

Topics: Adult; Arteriosclerosis; Diabetes Mellitus; Glycogen; Histocytochemistry; Humans; Leukemia; Microscopy, Electron; Middle Aged; Nephritis; Neurons; Retina; Retinitis

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Carbohydrates; Diabetes Mellitus; Glucose; Glycogen; Histocytochemistry; Humans; Insulin; Leukocytes; Lymphocytes; Pentosephosphates; Phagocytosis; Rats

Topics: Animals; Animals, Newborn; Antibiotics, Antineoplastic; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Fatty Acids, Nonesterified; Glucose Tolerance Test; Glycogen; Insulin; Ketone Bodies; Sheep; Triglycerides

Topics: Animals; Blood Glucose; Carbamates; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Experimental; Disease Models, Animal; Fasting; Glucosamine; Glycogen; Glycosuria; Guinea Pigs; Hyperglycemia; Hypoglycemia; Lactates; Liver Glycogen; Male; Mice; Nitroso Compounds; Obesity; Oxazoles; Phenformin; Pyridinium Compounds; Rats

Topics: Adult; Aged; Color; Cytoplasmic Granules; Diabetes Mellitus; Epithelium; Glycogen; Histocytochemistry; Humans; Iris; Male; Microscopy, Electron; Photography; Staining and Labeling

Topics: Animals; Diabetes Mellitus; Epinephrine; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Glycolysis; Insulin; Insulin Secretion; Islets of Langerhans; Methods; Mice; Obesity; Organ Size; Phosphoglycerate Kinase; Radioimmunoassay; Staining and Labeling

Topics: Adrenal Glands; Alcohol Oxidoreductases; Animals; Diabetes Mellitus; Dogs; Epinephrine; Esterases; Glucose-6-Phosphatase; Glycogen; Histocytochemistry; Lipids; Muscles; Pancreatectomy

Topics: Animals; Autoradiography; Blood Glucose; Cytoplasm; Diabetes Mellitus; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Guinea Pigs; Histological Techniques; Islets of Langerhans; Male; Mitosis; Prednisolone; Thymidine; Time Factors; Tritium

Topics: Acidosis; Animals; Blood Glucose; Cell Nucleus; Cricetinae; Cytoplasmic Granules; Diabetes Mellitus; Disease Models, Animal; Endoplasmic Reticulum; Glucagon; Glycogen; Golgi Apparatus; Insulin; Islets of Langerhans; Lysosomes; Male; Microscopy, Electron

Topics: Animals; Blood Glucose; Diabetes Mellitus; Female; Glycogen; Histocytochemistry; Insulin; Islets of Langerhans; Male; Mice; Microscopy, Electron

Topics: Adult; Basement Membrane; Biopsy; Chlorides; Diabetes Complications; Diabetes Mellitus; Edema; Glycogen; Humans; Magnesium; Methods; Microscopy, Electron; Middle Aged; Muscle Proteins; Muscles; Muscular Atrophy; Muscular Diseases; Phosphorus; Potassium; Sodium

Topics: Adult; Diabetes Mellitus; Gingiva; Glycogen; Humans; Oral Manifestations; Polysaccharides

Topics: Adult; Age Factors; Aged; Diabetes Mellitus; Gingiva; Glucuronates; Glycogen; Humans; Mannose; Middle Aged; Molecular Weight; Polysaccharides

Topics: Diabetes Mellitus; Epithelium; Glycogen; Humans; Iris; Male; Middle Aged; Photography

Topics: Adipose Tissue; Adrenalectomy; Animals; Blood Glucose; Carbon Isotopes; Chromatography, Gel; Diabetes Mellitus; Diaphragm; Fatty Acids, Nonesterified; Glucose; Glycogen; Humans; In Vitro Techniques; Insulin; Insulin Antibodies; Molecular Weight; Muscles; Rats; Stimulation, Chemical

Topics: Animals; Diabetes Mellitus; Dogs; Enzyme Activation; Glucagon; Glucosyltransferases; Glycogen; Infusions, Parenteral; Insulin; Liver; Magnesium; Metabolism; Pancreatectomy

Topics: Animals; Basement Membrane; Blood Glucose; Diabetes Mellitus; Diabetic Nephropathies; Disease Models, Animal; Glycogen; Golgi Apparatus; Lysosomes; Mice; Microscopy, Electron

Topics: Animals; Blood Glucose; Carbon; Carbon Dioxide; Carbon Isotopes; Diabetes Mellitus; Diabetes Mellitus, Experimental; Fasting; Glycogen; Glycosuria; Lipid Metabolism; Male; Proteins; Rats; Time Factors

Topics: Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glycogen; Humans; Insulin; Male; Middle Aged; Muscles

Topics: Aged; Biopsy; Cataract; Diabetes Complications; Diabetes Mellitus; Dupuytren Contracture; Electromyography; Female; Glycogen; Humans; Lactates; Male; Middle Aged; Muscles; Muscular Diseases; Physical Exertion; Transferases

Topics: Acetoacetates; Acetone; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glycogen; Hydroxybutyrates; Ketone Bodies; Lactation; Liver; Pregnancy

Topics: Adipose Tissue; Adrenal Glands; Animals; Antibiotics, Antineoplastic; Blood Glucose; Cell Membrane Permeability; Diabetes Mellitus; Diaphragm; Fasting; Fatty Acids, Nonesterified; Glycogen; Hypoglycemia; Insulin; Lipid Metabolism; Liver; Male; Muscles; Rats; Stimulation, Chemical

1. The influence of insulin on the metabolism of [1-(14)C]glucosamine by diaphragm muscle from normal rats and rats rendered diabetic with streptozotocin has been studied. 2. The glucosamine was converted into glucosamine 1-phosphate, glucosamine 6-phosphate, glycogen, lactate and small amounts of other unidentified intermediates. 3. Insulin increased the incorporation of (14)C into glycogen in both the normal and diabetic muscle, but did not increase the formation of the glucosamine phosphate esters. 4. The (14)C content in the glycogen was present partly as glucose and partly as glucosamine; there was significantly more [(14)C]glucose in the glycogen of the diabetic muscle than in that of the normal muscle.

Topics: Animals; Antibiotics, Antineoplastic; Carbon Isotopes; Diabetes Mellitus; Diaphragm; Glucosamine; Glucose; Glycogen; Hexosephosphates; In Vitro Techniques; Insulin; Lactates; Male; Metabolism; Muscles; Rats

Topics: Animals; Blood Glucose; Cricetinae; Diabetes Mellitus; Fasting; Glucose Tolerance Test; Glycogen; Hematocrit; Hemoglobins; Mice

Topics: Administration, Oral; Aged; Blood Glucose; Carbon Dioxide; Carboxylic Acids; Depression, Chemical; Diabetes Complications; Diabetes Mellitus; Diet; Diet Therapy; Dietary Carbohydrates; Evaluation Studies as Topic; Fasting; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycosuria; Humans; Hypoglycemic Agents; Insulin; Lipid Metabolism; Lipids; Metabolism; Muscles; Nutritional Physiological Phenomena; Pyrazoles; Time Factors; Triglycerides

Topics: Adult; Aged; Biopsy; Blood Glucose; Diabetes Mellitus; Dietary Carbohydrates; Fasting; Glucokinase; Glucose; Glycogen; Hexokinase; Humans; Insulin; Liver; Liver Glycogen; Male; Muscles; Spectrophotometry; Tolbutamide

Topics: Adrenal Cortex Hormones; Adrenalectomy; Animals; Atrophy; Blood Glucose; Diabetes Mellitus; Glycogen; Hyperglycemia; Hypoglycemia; Hypophysectomy; Insulin; Insulin Secretion; Islets of Langerhans; Liver Glycogen; Muscles; Myocardium; Necrosis; Rats; Staining and Labeling; Thyroidectomy; Thyroxine

Topics: Biopsy; Cell Nucleus; Chemical Phenomena; Chemistry; Diabetes Mellitus; Gluconeogenesis; Glycogen; Histocytochemistry; Humans; Liver; Liver Glycogen; Microscopy, Electron

Topics: Adult; Age Factors; Biopsy; Diabetes Mellitus; Glycogen; Histocytochemistry; Humans; Methods; Microscopy, Electron; Middle Aged; Muscle Proteins; Muscles; Nitrogen; Water-Electrolyte Balance

Topics: Acetone; Animals; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glycogen; Immune Sera; Insulin Antibodies; Liver Glycogen; Muscles; Rats

Topics: Acute Kidney Injury; Adult; Biopsy; Child; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose; Glycogen; Humans; Insulin; Male; Methods; Muscles; Peritoneal Dialysis; Shock, Surgical; Uremia; Water

Topics: Animals; Antibiotics, Antineoplastic; Blood Glucose; Citrates; Diabetes Mellitus; Diabetes Mellitus, Experimental; Fatty Acids, Nonesterified; Glycogen; Hexosephosphates; Injections, Intravenous; Ketones; Myocardium; Rats

Topics: Adenoma, Islet Cell; Adult; Aged; Blood Glucose; Child; Coloring Agents; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diazoxide; Glycogen; Glycolysis; Humans; Hyperglycemia; Injections, Intravenous; Insulin; Liver; Male; Middle Aged

Topics: Acid Phosphatase; Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Female; Glucose-6-Phosphatase; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glycogen; Glycosuria; Guinea Pigs; Histocytochemistry; Hydrocortisone; Islets of Langerhans; L-Lactate Dehydrogenase; Male; Time Factors

Topics: Antigens; Diabetes Mellitus; Diphtheria Toxoid; Energy Transfer; Escherichia coli; Exudates and Transudates; Glycogen; Histiocytes; Histocytochemistry; Humans; Inflammation; Insulin; Lymphocytes; Macrophages; Monocytes; Skin; Skin Window Technique

Topics: Blood Glucose; Dentistry; Diabetes Mellitus; Gingiva; Gingivitis; Glycogen

Three cases of nuclear glycogenosis in the liver of diabetic patients have been studied by electron microscopy. In addition to the glycogen deposits described by others, an unusual intranuclear glycogen-filled body was found in all three cases. This body occurred alone or in close contact with the major glycogen deposit.

Topics: Diabetes Complications; Diabetes Mellitus; Female; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Liver Diseases; Male; Microscopy, Electron

Topics: Adrenal Cortex Hormones; Age Factors; Diabetes Mellitus; Glucose; Glucose Tolerance Test; Glucosyltransferases; Glycogen; Humans; Insulin; Leukocytes; Uremia

1. The metabolism of [U-(14)C]glucose by the isolated diaphragm muscle of normal rats, rats rendered diabetic with streptozotocin and rats with transitory insulin deficiency after an injection of anti-insulin serum was studied. 2. The incorporation of [(14)C]glucose into glycogen and oligosaccharides was significantly decreased in the diabetic diaphragm muscle and in the muscle from rats treated with anti-insulin serum. 3. Neither diabetes nor transitory insulin deficiency influenced the oxidation of glucose, or the formation of lactate and hexose phosphate esters from glucose. 4. Insulin fully restored the incorporation of glucose into glycogen and maltotetraose in the diabetic muscle, but the incorporation into oligosaccharides, although increased in the presence of insulin, was significantly lower than the values obtained with normal diaphragm in the presence of insulin.

Topics: Animals; Antibiotics, Antineoplastic; Carbon Isotopes; Depression, Chemical; Diabetes Mellitus; Glucose; Glycogen; Hexosephosphates; Immune Sera; In Vitro Techniques; Insulin; Insulin Antibodies; Lactates; Muscles; Oligosaccharides; Rats

Topics: Adolescent; Adult; Aged; Anesthesia, Inhalation; Blood Glucose; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glycogen; Humans; Hypoglycemic Agents; Infant; Ketone Bodies; Male; Middle Aged; Preoperative Care; Surgical Procedures, Operative

Topics: Adult; Anemia, Hemolytic; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Female; Gastrointestinal Diseases; Gestational Age; Glycogen; Humans; Hyperthyroidism; Infant, Newborn; Liver Diseases; Neoplasms; Nephritis, Interstitial; Postpartum Period; Pregnancy; Respiratory Tract Diseases

Topics: Animals; Biological Assay; Carbon Isotopes; Chemical Phenomena; Chemistry; Culture Techniques; Diabetes Mellitus; Diaphragm; Endopeptidases; Glucose; Glycogen; Humans; Insulin; Rats; RNA

Topics: Adipose Tissue; Animals; Biological Assay; Carbon Isotopes; Diabetes Mellitus; Diaphragm; Epididymis; Glycogen; Humans; Injections, Intravenous; Insulin Antagonists; Male; Muscles; Rats; Serum Albumin

Topics: Adolescent; Adult; Age Factors; Aged; Alcoholism; Animals; Cell Nucleolus; Cell Nucleus; Child; Child, Preschool; Collagen; Cytoplasm; Cytoplasmic Granules; Diabetes Complications; Diabetes Mellitus; Diet, Diabetic; Female; Glycogen; Hepatitis; Hepatomegaly; Humans; Infant; Insulin; Liver Cirrhosis; Liver Function Tests; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria, Liver; Reticulum; Sex Factors; Splenomegaly; Sulfonamides

Topics: Animals; Biological Assay; Carbon Isotopes; Cattle; Diabetes Mellitus; Diaphragm; Endopeptidases; Glucose; Glycogen; Injections, Intraperitoneal; Insulin; Insulin Resistance; Pancreatic Extracts; Rats; Serum Albumin, Bovine

Topics: Diabetes Mellitus; Glycogen; Humans; Lectins; Leukemia, Lymphoid; Lymphocytes

Topics: Adult; Diabetes Mellitus; Female; Glycogen; Humans; Male; Middle Aged

Topics: Adipose Tissue; Animals; Blood Glucose; Carbon Isotopes; Diabetes Mellitus; Diaphragm; Fatty Acids, Nonesterified; Glucose; Glycerides; Glycogen; Male; Nicotinic Acids; Pyrazoles; Rats

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glucose; Glycogen; Histological Techniques; Hyperglycemia; Hypoglycemia; Injections, Intraperitoneal; Pancreas; Rats; Staining and Labeling

Topics: Animals; Diabetes Mellitus; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Guinea Pigs; Islets of Langerhans; Prednisolone

Topics: Animals; Cytoplasmic Granules; Diabetes Mellitus; Diet; Glycogen; Insulin; Islets of Langerhans; Microscopy, Electron; Proteins; Rats

Topics: Animals; Cytoplasmic Granules; Diabetes Mellitus; Glycogen; Hyperplasia; Islets of Langerhans; Mice; Microscopy, Electron; Polymorphism, Genetic; Species Specificity

Topics: Animals; Blood Glucose; Cricetinae; Diabetes Mellitus; Female; Glycogen; Glycosuria; Islets of Langerhans; Male; Prediabetic State

Topics: Animals; Capillaries; Cricetinae; Cytoplasmic Granules; Diabetes Mellitus; Female; Glycogen; Islets of Langerhans; Male; Microscopy, Electron

Topics: Diabetes Mellitus; Female; Glycogen; Humans; Male; Pregnancy

Topics: Anesthesia; Carbohydrate Metabolism; Diabetes Mellitus; Glucose; Glycogen; Humans; Surgical Procedures, Operative

Topics: Adult; Asthma; Blood Glucose; Cortisone; Diabetes Complications; Diabetes Mellitus; Glucose Tolerance Test; Glycogen; Humans; Insulin; Lipase; Middle Aged

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Fructose; Glucose; Glycogen; Humans; Infusions, Parenteral; Ribose

Topics: Animals; Diabetes Mellitus; Dogs; Enzymes; Glycogen; Histocytochemistry; Microscopy, Electron; Muscular Diseases; Neoplasms, Experimental; Rabbits

Topics: Adrenal Glands; Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Duodenum; Esterases; Female; Glycogen; Histocytochemistry; Indicators and Reagents; Kidney; Liver; Liver Glycogen; Male; Muscles; Oxidoreductases; Phosphoric Monoester Hydrolases; Phosphotransferases; Rabbits

Topics: Diabetes Mellitus; Fatty Acids; Glucose; Glycogen; Humans; Obesity

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diet; Glycogen; Insulin; Islets of Langerhans; Ketone Bodies; Microscopy, Electron; Protein Biosynthesis; Rats

Topics: Adult; Aged; Diabetes Mellitus; Diet, Diabetic; Female; Glycogen; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glucagon; Glycogen; Humans; Hyperglycemia; Insulin; Liver; Liver Glycogen; Pharmacology; Rabbits

Topics: Antimetabolites; Biochemical Phenomena; Biochemistry; Biological Assay; Diabetes Mellitus; Diaphragm; Fatty Acids; Glucose; Glycogen; Humans; Insulin; Insulin Antagonists; Iodine Isotopes; Rats; Research; Serum Albumin

Topics: Blood Glucose; Carbohydrate Metabolism; Carbon Dioxide; Diabetes Mellitus; Geriatrics; Glucose; Glycogen; In Vitro Techniques; Insulin; Leukocytes; Metabolism; Oxygen; Pyruvates

Topics: Absorption; Acidosis; Amylases; Biomedical Research; Blood Glucose; Coloring Agents; Diabetes Mellitus; Fibrinogen; Glycogen; Glycosuria; Heparin; Histocytochemistry; Humans; Insulin; Leukocytes; Neutrophils; Periodic Acid; Pharmacology; Research; Spectrophotometry; Staining and Labeling; Sulfuric Acids

Topics: Adipose Tissue; Animals; Blood Glucose; Carbon Isotopes; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dogs; Epididymis; Fatty Acids; Fatty Acids, Nonesterified; Glucose; Glycerides; Glycerol; Glycogen; Humans; Immune Sera; Insulin Antibodies; Lipid Metabolism; Lipids; Liver Glycogen; Male; Mice; Palmitic Acid; Rats; Research; Toxicology

Topics: Adolescent; Adrenal Glands; Blood Glucose; Carbohydrate Metabolism; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Glucose; Glycogen; Humans; Hypoglycemia; Infant; Insulin; Insulin Antagonists; Maternal-Fetal Exchange; Pituitary Gland; Pregnancy

Topics: Adipose Tissue; Animals; Calcium; Carbohydrate Metabolism; Carbon Dioxide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Dwarfism; Dwarfism, Pituitary; Fatty Acids; Glycerides; Glycogen; Growth Hormone; Hypopituitarism; Kidney Function Tests; Leucine; Lipid Metabolism; Metabolism; Pharmacology; Primates; Prolactin; Research; Sheep

Topics: Aged; Diabetes Mellitus; Glycogen; Humans; In Vitro Techniques; Male; Mouth Mucosa; Staining and Labeling

Topics: Diabetes Mellitus; Glycogen; Humans; Liver; Liver Glycogen

Topics: Animals; Diabetes Mellitus; Dogs; Glucagon-Secreting Cells; Glycogen; Growth Hormone; Human Growth Hormone; Humans; Islets of Langerhans

Topics: Animals; Diabetes Mellitus; Dogs; Glycogen; Growth Hormone; Humans; Islets of Langerhans

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Extraembryonic Membranes; Female; Glycogen; Humans; Placenta; Pregnancy; Pregnancy in Diabetics

Topics: Acidosis; Acidosis, Lactic; Blood Chemical Analysis; Carbohydrate Metabolism; Diabetes Mellitus; Glycogen; Humans; Lactates; Metabolism

Topics: Coloring Agents; Diabetes Mellitus; Glycogen; Humans; Indicators and Reagents; Leukocyte Count; Leukocytes; Periodic Acid; Rosaniline Dyes; Staining and Labeling

Topics: Adrenal Glands; Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Hyperglycemia; Hypoglycemia; Pituitary Gland; Rats

Topics: Child; Diabetes Mellitus; Edema; Edetic Acid; Glycogen; Heart Failure; Humans; Infant

Topics: Diabetes Mellitus; Glycogen; Humans; Leukocytes

Topics: Animals; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Experimental; Female; Glycogen; Glycogenolysis; Islands; Islets of Langerhans; Pregnancy; Rats

Topics: Carbutamide; Catheterization; Diabetes Mellitus; Glucagon; Glycogen; Glycogenolysis; Humans; Liver

Topics: Animals; Cholesterol; Diabetes Mellitus; Fats; Glycogen; Insulin; Lipid Metabolism; Lipogenesis; Liver; Rats

Topics: Diabetes Complications; Diabetes Mellitus; Glucagon; Glycogen; Humans; Liver Diseases

Topics: Diabetes Mellitus; Gastrointestinal Tract; Glycogen; Glycogenolysis; Humans; Liver; Liver Glycogen; Neoplasms

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Glycogen; Humans; Leukocytes

Topics: Child; Diabetes Mellitus; Female; Glycogen; Heart Diseases; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Metabolic Diseases; Mothers; Pregnancy

Topics: Diabetes Mellitus; Female; Glycogen; Humans; Mothers; Placenta; Pregnancy

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Glycogenolysis; Liver; Liver Glycogen

Topics: Diabetes Mellitus; Glycogen; Leukocytes; Sulfanilamide; Sulfanilamides; Urea

Topics: Diabetes Mellitus; Glycogen; Insulin; Liver

Topics: Blood Glucose; Catabolite Repression; Diabetes Mellitus; Epinephrine; Glucose; Glycogen; Humans; Insulin; Leukocytes; Pharmaceutical Preparations

Topics: Diabetes Mellitus; Glycogen; Humans; Liver

Topics: Animals; Carbohydrate Metabolism; Carbon; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glucose; Glycogen; Glycogenolysis; Liver; Pyruvates; Pyruvic Acid; Rats

Topics: Diabetes Mellitus; Glycogen; Humans; Leukocytes

Topics: Animals; Diabetes Mellitus; Glycogen; Glycogenolysis; Liver; Liver Glycogen

Topics: Diabetes Mellitus; Glycogen; Glycogenolysis; Humans; Insulin; Insulin Resistance; Liver

Topics: Animals; Blood; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Humans

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Glycogen; Humans; Insulin; Leukocytes

Topics: Carbohydrate Metabolism; Coenzymes; Diabetes Mellitus; Glucose; Glycogen; Hexosephosphates; Hexoses; Humans; Insulin; Insulins; Pyruvates

Topics: Diabetes Mellitus; Glycogen; Humans; Liver Glycogen

Topics: Animals; Biomedical Research; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Humans; Hyperglycemia; Pancreas; Rabbits

Topics: Carbohydrate Metabolism; Carbohydrates; Diabetes Mellitus; Glycogen; Humans; Sweetening Agents

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Humans; Liver; Rabbits

Topics: Diabetes Mellitus; Glycogen; Liver

Topics: Acetoacetates; Carbohydrate Metabolism; Diabetes Mellitus; Glucose; Glycogen; Humans; Injections; Insulin

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Gingiva; Gingival Diseases; Glycogen; Humans; Periodontal Diseases

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Enzymes; Glycogen; Glycolysis; Liver; Rats; Succinate Dehydrogenase

Topics: Alloxan; Animals; Diabetes Mellitus; Glycogen; Liver; Rats

Topics: Animals; Blood; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Humans; Leukocytes

Topics: Amino Acid Metabolism, Inborn Errors; Amino Acids; Cystinosis; Diabetes Mellitus; Dwarfism; Glycogen; Urine; Urologic Diseases

Topics: Adrenal Cortex; Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Liver Glycogen; Rats; Tissue Extracts

Topics: Diabetes Mellitus; Glycogen; Hepatitis; Humans

Topics: Diabetes Mellitus; Epinephrine; Glycogen; Hepatitis; Humans

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Gluconeogenesis; Glycogen; Humans; Insulin; Kidney

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Humans; Liver; Liver Glycogen; Muscles; Needles

Topics: Diabetes Complications; Diabetes Mellitus; Glycogen; Glycogen Storage Disease; Humans

Topics: Diabetes Mellitus; Glycogen; Liver; Muscles; Thiamine; Thiazoles; Tissues

Two hundred and seven albino rats were injected subcutaneously with alloxan in doses varying from 140 to 200 mg. per cent per kilo of body weight. Fifty-nine animals which developed hyperglycemia (blood sugar levels above 150 mg. per cent) were observed for periods from 5 days to 32 weeks. Postmortem examination of the kidneys of these diabetic animals revealed glycogen deposition in the loops of Henle and convoluted tubules in 26 rats or 44 per cent. Glycogen could not be demonstrated in the glomeruli. Within the time limits of this experiment (32 weeks) no intercapillary glomerulosclerosis was observed. The following facts were revealed regarding glycogen nephrosis in alloxan diabetes: (a) Its appearance in the kidneys of the diabetic rats depended solely upon the terminal blood sugar levels of these animals. A value of 350 mg. per cent was the critical level, above which glycogen nephrosis was almost invariably demonstrable. With terminal levels below 300 mg. per cent no glycogen nephrosis was found. (b) No relationship existed between the postmortem finding of glycogen nephrosis and the initial blood sugar level, or the maximum height of the hyperglycemia attained by individual rats. (c) The results suggest that glycogen nephrosis is a reversible lesion.

Topics: Alloxan; Animals; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Hyperglycemia; Kidney; Kidney Diseases; Kidney Tubules; Nephrosis

Topics: Acidosis; Biopsy; Diabetes Mellitus; Diabetic Ketoacidosis; Glycogen; Humans; Liver; Liver Glycogen

Topics: Diabetes Mellitus; Glycogen; Liver; Liver Glycogen

Topics: Diabetes Mellitus; Glycogen; Glycogenolysis; Humans

Topics: Child; Diabetes Complications; Diabetes Mellitus; Dwarfism; Glycogen; Hepatomegaly; Humans; Infant; Obesity

Topics: Child; Diabetes Complications; Diabetes Mellitus; Dwarfism; Glycogen; Hepatomegaly; Humans; Infant; Obesity

Topics: Diabetes Mellitus; Glycogen; Glycogenolysis; Heredity; Humans

Topics: Animals; Carbohydrate Metabolism; Deuterium; Diabetes Mellitus; Glucose; Glycogen; Humans; Rabbits

Topics: Alloxan; Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Liver; Muscles; Rats

Topics: Alloxan; Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Glycogen; Liver; Liver Glycogen; Muscles; Rats