glycogen and Prediabetic-State

Hepatalin is a hormone secreted by the liver in response to pulses of insulin after a mixed nutrient meal, but only if the liver receives two permissive synergistic feeding signals from the stomach. Hepatalin stimulates glucose uptake and storage as glycogen in skeletal muscle, heart, and kidney but not liver, intestines, or adipocytes. Insulin acts primarily on liver and fat. Reduced hepatalin action results in postprandial hyperglycemia, compensatory elevation of insulin secretion, and a resultant shift in partitioning of nutrient energy storage from glycogen in muscle, to fat. Chronic hepatalin suppression leads to a predictable chronology of dysfunctions, first diagnosable as Absence of Meal-induced Insulin Sensitization (AMIS) which progresses to prediabetes, adiposity, and type 2 diabetes. The focus on nutrient partitioning and the role of hepatalin allows AMIS to be diagnosed, prevented, and treated, including through the use of lifestyle interventions.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycogen; Humans; Insulin; Insulin Resistance; Muscle, Skeletal; Obesity; Prediabetic State

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; 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

This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O

Topics: Adult; Anaerobic Threshold; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Glucose Tolerance Test; Glucose Transporter Type 4; Glycogen; Humans; Hypoxia; Insulin; Lipids; Male; Muscle, Skeletal; Prediabetic State

A prediabetic population has an increased risk of cognitive decline and type 2 diabetes mellitus (T2DM). This study investigated whether the progression of memory dysfunction and dysregulated brain glycogen metabolism is prevented with 4 mo of exercise intervention from the presymptomatic stage in a T2DM rat model. Memory function and biochemical and molecular profiles were assessed in the presymptomatic stage of Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a T2DM model, with Long-Evans Tokushima (LETO) rats as genetic control. These rats were subjected to light- or moderate-intensity treadmill running for 4 mo with repetition of the same experiments. Significant hippocampal-dependent memory dysfunction was observed in the presymptomatic stage of OLETF rats, accompanied by downregulated levels of hippocampal monocarboxylate transporter 2 (MCT2), a neuronal lactate-transporter, without alteration in hippocampal glycogen levels. Four months of light or moderate exercise from the presymptomatic stage of T2DM normalized glycemic parameters and hippocampal molecular normalization through MCT2, glycogen, and brain-derived neurotrophic factor (BDNF) levels with the improvement of memory dysfunction in OLETF rats. A 4-mo exercise regimen from the presymptomatic stage of T2DM at a light and moderate intensities contributed to the prevention of the development of T2DM and the progression of cognitive decline with hippocampal lactate-transport and BDNF improvement.

Topics: Animals; Blood Glucose; Brain-Derived Neurotrophic Factor; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glycogen; Hippocampus; Humans; Lactates; Physical Conditioning, Animal; Prediabetic State; Rats; Rats, Inbred OLETF; Rats, Long-Evans

The regulation of microRNAs (miRNAs) at different stages of the progression of type 2 diabetes mellitus (T2DM) and their role in glucose homeostasis was investigated.. Microarrays were used to assess miRNA expression in skeletal muscle biopsies taken from healthy individuals and patients with pre-diabetes or T2DM, and insulin resistant offspring of rat dams fed a high fat diet during pregnancy.. Twenty-three miRNAs were differentially expressed in patients with T2DM, and 7 in the insulin resistant rat offspring compared to their controls. Among these, only one miRNA was similarly regulated: miR-194 expression was significantly reduced by 25 to 50% in both the rat model and in human with pre-diabetes and established diabetes. Knockdown of miR-194 in L6 skeletal muscle cells induced an increase in basal and insulin-stimulated glucose uptake and glycogen synthesis. This occurred in conjunction with an increased glycolysis, indicated by elevated lactate production. Moreover, oxidative capacity was also increased as we found an enhanced glucose oxidation in presence of the mitochondrial uncoupler FCCP. When miR-194 was down-regulated in vitro, western blot analysis showed an increased phosphorylation of AKT and GSK3β in response to insulin, and an increase in expression of proteins controlling mitochondrial oxidative phosphorylation.. Type 2 diabetes mellitus is associated with regulation of several miRNAs in skeletal muscle. Interestingly, miR-194 was a unique miRNA that appeared regulated across different stages of the disease progression, from the early stages of insulin resistance to the development of T2DM. We have shown miR-194 is involved in multiple aspects of skeletal muscle glucose metabolism from uptake, through to glycolysis, glycogenesis and glucose oxidation, potentially via mechanisms involving AKT, GSK3 and oxidative phosphorylation. MiR-194 could be down-regulated in patients with early features of diabetes as an adaptive response to facilitate tissue glucose uptake and metabolism in the face of insulin resistance.

Topics: Animals; Cell Line; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Female; Gene Expression Regulation; Glucose; Glycogen; Glycogen Synthase Kinase 3; Humans; Insulin; Insulin Resistance; Male; Mice, Inbred C57BL; MicroRNAs; Mitochondria; Muscle, Skeletal; Myoblasts; Oxidative Phosphorylation; Prediabetic State; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-α in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes.

Topics: Adipose Tissue, White; Angelica sinensis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 2; Glycogen; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Lipid Metabolism Disorders; Liver; Male; Mice, Inbred BALB C; Muscle, Skeletal; Pancreas; Plant Roots; Polysaccharides; Prediabetic State; Random Allocation

The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus.

Topics: Animals; Blotting, Western; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Estradiol; Gene Expression; Glucose; Glycogen; Inhibins; Male; Prediabetic State; Rats; Rats, Wistar; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; Sertoli Cells; Testis; Testosterone

Dietary trans-fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high-fat saturated diets, relative to low-fat diets, induce adiposity and whole-body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low-fat diet containing elaidic acid (18:1t), the predominant trans-fatty acid isomer found in the human food supply. Male 8-week-old Sprague-Dawley rats were fed a 10% trans-fatty acid enriched (LF-trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (1H-MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic-hyperinsulinemic clamps (week 8) determined whole-body and tissue-specific insulin sensitivity followed by high-resolution ex vivo 1H-NMR to assess tissue biochemistry. Rats fed the LF-trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low-fat control diet. Net glycogen synthesis was also increased in the LF-trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF-trans diet, whereas in rats fed a 45% saturated fat (HF-sat) diet, impaired glucose disposal corresponded to increased IMCLTA. Neither diet induced an increase in IMCLsoleus. These findings imply that trans-fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans-fatty acids induce insulin resistance differs from diets enriched with saturated fats.

Topics: Adiposity; Animals; Blood Glucose; Diet, Fat-Restricted; Energy Intake; Energy Metabolism; Glucose Clamp Technique; Glycogen; Hyperphagia; Insulin; Insulin Resistance; Intra-Abdominal Fat; Liver; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Muscle, Skeletal; Obesity; Oleic Acid; Oleic Acids; Prediabetic State; Rats; Rats, Sprague-Dawley; Time Factors; Trans Fatty Acids

Sutherlandia frutescens has been marked as a potential hypoglycaemic agent for the treatment of type 2 diabetes. We investigated the effects of Sutherlandia frutescens in bringing about hypoglycaemia and promoting glucose uptake in pre-diabetic rats. Crushed Sutherlandia frutescens leaves in drinking water were administered to rats fed a high fat diet. Positive control rats received only metformin. Glucose uptake experiments were undertaken using [(3)H] deoxy-glucose. Various physiological parameters were also measured. Rats receiving Sutherlandia frutescens displayed normoinsulinaemic levels, after 8 weeks medicational compliance, compared to the fatty controls. There was a significant increase in glucose uptake into muscle and adipose tissue, and a significant decrease in intestinal glucose uptake (p<0.001 at 60min) in rats receiving the plant extract. The Sutherlandia frutescens plant extract shows promise as a type 2 anti-diabetes medication because of its ability to normalize insulin levels and glucose uptake in peripheral tissues and suppress intestinal glucose uptake, with no weight gain noted. The exact mechanism of action and the extract's efficacy in humans need further confirmation.

Topics: Anesthesia; Animals; Blood Glucose; Body Weight; Diet; Dietary Fats; Glucose; Glycogen; Hyperinsulinism; Hypoglycemic Agents; Insulin; Intestinal Mucosa; Male; Metformin; Plant Extracts; Plants, Medicinal; Prediabetic State; Rats; Rats, Wistar

Pre-diabetic subjects with high insulin secretory capacity have double risk of cardiovascular disease compared with subjects who do not develop insulin-resistance. It is well established that the ability of the myocardium to increase its glycolytic ATP production plays a crucial role in determining cell survival under conditions of ischemia. Up to now, whether the pre-diabetic state reduces the tolerance of the heart to ischemia by affecting its ability to increase its energy production through glycolysis remains unknown. The aim of the present study was to assess whether insulin resistance affects the ability of the myocardium to increase glycolysis under ischemic conditions. Male Wistar rats were fed for 8 weeks a fructose-enriched (33%) diet to induce a pre-diabetic state. Hearts were isolated and subjected to ex-vivo low-flow (2%) ischemia for 30 min. The fructose diet increased sarcolemmal GLUT4 localisation in myocardial cells under basal conditions compared with controls. This effect was not accompanied by increased glucose utilisation. Ischemia induced the translocation of GLUT4 to the plasma membrane in controls but did not significantly modify the distribution of these transporters in pre-diabetic hearts. Glycolytic flux under ischemic conditions was significantly lower in fructose-fed rat hearts compared with controls. The reduction of glycolytic flux during ischemia in fructose-fed rat hearts was not due to metabolic inhibition downstream hexokinase II since no cardiac accumulation of glucose-6-phosphate was detected. In conclusion, our results suggest that the pre-diabetic state reduces the tolerance of the myocardium to ischemia by decreasing glycolytic flux adaptation.

Topics: Adaptation, Physiological; Animals; Diabetes Mellitus, Experimental; Fructose; Glucose; Glucose Transporter Type 4; Glycogen; Glycolysis; Hexosephosphates; In Vitro Techniques; Insulin Resistance; Lactic Acid; Male; Monosaccharide Transport Proteins; Muscle Proteins; Myocardial Ischemia; Myocardium; Myocytes, Cardiac; Prediabetic State; Protein Transport; Rats; Rats, Wistar; Sarcolemma

The investigations were in 6 prediabetic and 8 normoglycemic sand rats carried out with a histochemical method (PAS-reaction). Glycogen is present in pancreatic acinar cells in various quantity. It is in the cytoplasm homogenously distributed. The PAS positive acini are near the islets of Langerhans localized, which have in their B cells also glycogen deposites. The phenomenon is by the vascularisation of the pancreas explained.

Topics: Animals; Glycogen; Pancreas; Prediabetic State; Rodentia

Topics: Adult; Biopsy; Blood Glucose; Diabetes Mellitus; Ear, External; Glycogen; Humans; Middle Aged; Periodic Acid; Prediabetic State; Skin; 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: Adipose Tissue; Adolescent; Age Factors; Animals; Biological Assay; Carbon Isotopes; Child; Child, Preschool; Diaphragm; Female; Glucose Tolerance Test; Glycogen; Humans; Insulin; Insulin Secretion; Lipodystrophy; Male; Muscles; Prediabetic State; Puberty; Rats; Syndrome; Time Factors

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

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

Topics: Age Factors; Aged; Arteriosclerosis; Blood Pressure; Body Weight; Carbohydrate Metabolism; Cholesterol; Fatty Acids, Nonesterified; Glucose Tolerance Test; Glycogen; Humans; Lipid Metabolism; Male; Middle Aged; Prediabetic State; Triglycerides; Uric Acid

Topics: Female; Gestational Age; Glycogen; Humans; Postpartum Period; Prediabetic State; Pregnancy

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