glycogen and Hyperlipidemias

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adipose Tissue; Animals; Biguanides; Biological Transport; Carbon Dioxide; Carbon Radioisotopes; Diabetes Mellitus, Experimental; Fatty Acids; Gluconeogenesis; Glycerol; Glycogen; Guinea Pigs; Humans; Hyperlipidemias; Insulin; Liver; Malate Dehydrogenase; Muscles; Oxidation-Reduction; Perfusion; Phenformin; Pyruvate Carboxylase; Rats; Species Specificity

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

Topics: Animals; Arteriosclerosis; Cholesterol; Fatty Acids, Nonesterified; Glycogen; Humans; Hyperlipidemias; Nephrotic Syndrome; Thyroxine; Triglycerides

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 ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer induced ER-stress markers in the liver, however cachexia progression further deteriorated liver ER-stress, disrupted protein synthesis regulation and caused a differential inflammatory response related to STAT-3 and NF-κB (Nuclear factor-κB) signaling.

Topics: Animals; Cachexia; Endoplasmic Reticulum Stress; Genes, APC; Glycogen; Hyperlipidemias; Inflammation; Insulin Resistance; Lipid Metabolism; Liver; Mice; NF-kappa B; Protein Biosynthesis; Signal Transduction; STAT3 Transcription Factor

Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia.. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared.. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state.. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.

Topics: Animals; Blood Glucose; Body Weight; Carrageenan; Diet; Diet, High-Fat; Disease Models, Animal; Dyslipidemias; Food Additives; Food Deprivation; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Glycogen; Hyperglycemia; Hyperlipidemias; Inflammation; Lipids; Male; Mice; Mice, Inbred C57BL; Risk Factors

In the liver, insulin-mediated activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is at the core of metabolic control. Multiple PI3K and Akt isoenzymes are found in hepatocytes and whether isoform-selective interplays exist is currently unclear. Here we report that insulin signalling triggers the association of the liver-specific class II PI3K isoform γ (PI3K-C2γ) with Rab5-GTP, and its recruitment to Rab5-positive early endosomes. In these vesicles, PI3K-C2γ produces a phosphatidylinositol-3,4-bisphosphate pool specifically required for delayed and sustained endosomal Akt2 stimulation. Accordingly, loss of PI3K-C2γ does not affect insulin-dependent Akt1 activation as well as S6K and FoxO1-3 phosphorylation, but selectively reduces Akt2 activation, which specifically inhibits glycogen synthase activity. As a consequence, PI3K-C2γ-deficient mice display severely reduced liver accumulation of glycogen and develop hyperlipidemia, adiposity as well as insulin resistance with age or after consumption of a high-fat diet. Our data indicate PI3K-C2γ supports an isoenzyme-specific forking of insulin-mediated signal transduction to an endosomal pool of Akt2, required for glucose homeostasis.

Topics: Adiposity; Aging; Animals; Diet, High-Fat; Endosomes; Forkhead Transcription Factors; Glucose; Glycogen; Glycogen Synthase; Hepatocytes; Homeostasis; Hyperlipidemias; Insulin; Insulin Resistance; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Proto-Oncogene Proteins c-akt; rab5 GTP-Binding Proteins; Ribosomal Protein S6 Kinases; Signal Transduction

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress.

Topics: Alloxan; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Female; Flow Cytometry; Glutathione; Glycogen; Hyperglycemia; Hyperlipidemias; Insulin; Lipids; Liver; Male; Malondialdehyde; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; N-Acetylneuraminic Acid; Nitric Oxide; Oxidative Stress; Pancreas; Rats, Wistar; Vitamin E

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia and other symptoms like polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger) which ultimately causes various other complications like retinopathy, neuropathy, nephropathy and microangiopathy.. The antidiabetic and antihyperlipidemic potential of oil from Piper longum (PLO) and piperine was investigated with their possible mechanism using α-glucosidase, aldose reductase (AR), and pancreatic lipase inhibitory activity.. The biochemical parameters, viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride, and antioxidant parameters, were estimated for all treated groups in acute and chronic antihyperglycemic animal models.. PLO (100 and 200 mg/kg), piperine (25 and 50 mg/kg), and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin, and high-density lipoprotein and decrease in glycosylated hemoglobin, triglyceride, and total plasma cholesterol in PLO-administered groups as compared to control group. The IC50 value of PLO for α-glucosidase, AR, and pancreatic lipase was found to be 150 ± 2.5, 120 ± 1.2, and 175 ± 1.2 μg/ml, respectively, which was found comparable with the standard drugs acarbose (90 ± 2.3 μg/ml), quercetin (80 ± 2.3 μg/ml), and orlistat (25 ± 0.5 μg/ml), respectively.. The investigation done reveals that PLO has significant antidiabetic and antihyperlipidemic activity.

Topics: Aldehyde Reductase; Alkaloids; alpha-Glucosidases; Animals; Benzodioxoles; Blood Glucose; Cholesterol; Diabetes Mellitus, Experimental; Glutathione; Glycogen; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Lipase; Liver; Piper; Piperidines; Plant Oils; Polyunsaturated Alkamides; Rats; Rats, Wistar; Triglycerides

Aging is closely associated with muscle insulin resistance, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. We examined the hypothesis that muscle insulin resistance in healthy aging promotes increased hepatic de novo lipogenesis (DNL) and hyperlipidemia by altering the distribution pattern of postprandial energy storage. Healthy, normal weight, sedentary elderly subjects pair-matched to young subjects were given two high-carbohydrate meals followed by ¹³C/¹H magnetic resonance spectroscopy measurements of postprandial changes in muscle and liver glycogen and lipid content, and assessment of DNL using ²H₂O. Net muscle glycogen synthesis was reduced by 45% (P < 0.007) in the elderly subjects compared with the young, reflecting severe muscle insulin resistance. Net liver glycogen synthesis was similar between groups (elderly, 143 ± 23 mmol/L vs. young, 138 ± 13 mmol/L; P = NS). Hepatic DNL was more than twofold higher in the elderly than in the young subjects (elderly, 14.5 ± 1.4% vs. young, 6.9 ± 0.7%; P = 0.00015) and was associated with approximately threefold higher postprandial hepatic triglyceride (TG) content (P < 0.005) and increased fasting plasma TGs (elderly, 1.19 ± 0.18 mmol/L vs. young, 0.74 ± 0.11 mmol/L; P = 0.02). These results strongly support the hypothesis that muscle insulin resistance in aging promotes hyperlipidemia and NAFLD by altering the pattern of postprandial carbohydrate storage away from muscle glycogen and into hepatic DNL.

Topics: Adult; Aged; Aging; Dietary Carbohydrates; Fatty Liver; Female; Glycogen; Humans; Hyperlipidemias; Insulin Resistance; Lipogenesis; Liver; Male; Metabolic Syndrome; Muscle, Skeletal; Non-alcoholic Fatty Liver Disease; Postprandial Period; Triglycerides; Young Adult

In this study we evaluated the hyperglycemic and hyperlipidemic effects of chlorpyrifos (CPF) after an acute exposure in rats. The mechanisms involved in hyperglycemia induced by CPF were studied. A single dose of CPF (50 mg kg(-1), subcutaneous, s.c.) was administered to overnight-fasted rats. Glucose and corticosterone levels, lipid status and paraoxonase (PON1) activity were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels, tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was also determined. CPF caused an increase in glucose and glycogen levels as well as in TAT and G6Pase activities. The CPF exposure caused an increase in corticosterone levels, an inhibition of AChE activity and a reduction of PON1 activity. Regarding the lipid status, CPF induced an increase in triglycerides (TG) and low-density lipoprotein-cholesterol (LDL) levels and a decrease in high-density lipoprotein (HDL) levels associated with an increase of cardiovascular risk factors and the atherogenic index. The present study demonstrated that a single CPF administration caused hyperglycemia and hyperlipidemia in rats. The activation of the gluconeogenesis pathway, probably elicited by hypercorticosteronemia, is involved in the hyperglycemic effect of CPF in rats.

Topics: Acetylcholinesterase; Animals; Aryldialkylphosphatase; Blood Glucose; Chlorpyrifos; Corticosterone; Environmental Pollutants; Glucose-6-Phosphatase; Glycogen; GPI-Linked Proteins; Hyperglycemia; Hyperlipidemias; Lipids; Male; Rats; Rats, Wistar; Toxicity Tests, Acute; Tyrosine Transaminase

Malnutrition in utero can "program" the fetal tissues, making them more vulnerable to metabolic disturbances. Also there is association between excessive consumption of fructose and the development of metabolic syndrome. However, there is little information regarding the acute effect of physical exercise on subjects recovered from malnutrition and/or fed with a fructose-rich diet. The objective of this study was to evaluate the metabolic aspects and the response to acute physical exercise in rats recovered from fetal protein malnutrition with a fructose-rich diet.. Pregnant Wistar rats were fed with a balanced (B) diet or a low-protein (L) diet. After birth and until 60 days of age, the offspring were distributed into four groups according to the diet received: B: B diet during the whole experiment; balanced/fructose (BF): B diet until birth and fructose-rich (F) diet afterwards; low protein/balanced (LB): L diet until birth and B diet afterwards; low protein/fructose (LF): L diet until birth and F diet afterwards.. The excess fructose intake reduced the body weight gain, especially in the BF group. Furthermore, the serum total cholesterol and the LDL cholesterol were elevated in this group. In the LF group, the serum total cholesterol and the muscle glycogen increased. Acute physical exercise increased the serum concentrations of glucose, triglycerides, HDL cholesterol and liver lipids and reduced the concentrations of muscle glycogen in all groups.. An excess fructose intake induced some signs of metabolic syndrome. However, protein malnutrition appeared to protect against the short term effects of fructose. In other hand, most responses to acute physical exercise were not influenced by early malnutrition and/or by the fructose overload.

Topics: Animals; Animals, Newborn; Female; Fructose; Glycogen; Hyperglycemia; Hyperlipidemias; Lactation; Lipid Metabolism; Liver; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Motor Activity; Muscle, Skeletal; Pregnancy; Protein Deficiency; Rats; Rats, Wistar; Weight Gain

To evaluate the antidiabetic and antioxidant effects of various fractions of Phyllanthus simplex on alloxan induced diabetes in rats.. Hypoglycemic effect of Phyllanthus simplex fractions was evaluated in normal and diabetic rats. Diabetes was induced by intraperitoneal injection of alloxan monohydrate (120 mg/kg). Normal and diabetic rats were divided into different groups (six rats each group) and orally administered with petroleum ether (P.E.) (200 and 400 mg/kg), ethyl acetate (EtOAc) (100 and 200 mg/kg), methanol (125 and 250 mg/kg), water fraction (150 and 300 mg/kg) and glibenclamide (10 mg/kg) for 21 days. Blood samples were collected from overnight fasted normal rats on day 21, from overnight fasted diabetic rats at 7, 14 and 21 days of treatment and analyzed for blood glucose level. On day 22 blood samples were collected from diabetic rats to estimate biochemical parameters, rats were sacrificed by single stunning and tissues were excised to measure their antioxidant and glycogen status.. In the normoglycemic rats, MeOH (125 and 250 mg/kg) and aqueous fractions (150 and 300 mg/kg) showed a significant (P<0.05) hypoglycemic effect on day 21. In diabetic control rats, MeOH (125 and 250 mg/kg) and aqueous fractions (150 and 300 mg/kg) showed significant antihyperglycemic effect (P<0.001). The active fractions (MeOH and aqueous) of Phyllanthus simplex also increased the body weight of diabetic rats significantly compared to the control group. The active fractions were able to normalize the marked alterations in antioxidant enzymes and antioxidant parameters levels in liver and kidney. Treatment with the active fractions also normalized the diabetic induced hyperlipidemia and liver glycogen.. These results demonstrate the antidiabetic and antioxidant potential of fractions of Phyllanthus simplex and suggests that the plant may have therapeutic value in diabetes and related complications.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Glycogen; Hyperlipidemias; Hypoglycemic Agents; Kidney; Liver; Male; Phyllanthus; Phytotherapy; Plant Extracts; Rats

MAPKs are crucial for TNF-alpha and IL-6 production by innate immune cells in response to TLR ligands. MAPK phosphatase 1 (Mkp-1) deactivates p38 and JNK, abrogating the inflammatory response. We have previously demonstrated that Mkp-1(-/-) mice exhibit exacerbated inflammatory cytokine production and increased mortality in response to challenge with LPS and heat-killed Staphylococcus aureus. However, the function of Mkp-1 in host defense during live Gram-negative bacterial infection remains unclear. We challenged Mkp-1(+/+) and Mkp-1(-/-) mice with live Escherichia coli i.v. to examine the effects of Mkp-1 deficiency on animal survival, bacterial clearance, metabolic activity, and cytokine production. We found that Mkp-1 deficiency predisposed animals to accelerated mortality and was associated with more robust production of TNF-alpha, IL-6 and IL-10, greater bacterial burden, altered cyclooxygenase-2 and iNOS expression, and substantial changes in the mobilization of energy stores. Likewise, knockout of Mkp-1 also sensitized mice to sepsis caused by cecal ligation and puncture. IL-10 inhibition by neutralizing Ab or genetic deletion alleviated increased bacterial burden. Treatment with the bactericidal antibiotic gentamicin, given 3 h after Escherichia coli infection, protected Mkp-1(+/+) mice from septic shock but had no effect on Mkp-1(-/-) mice. Thus, during Gram-negative bacterial sepsis Mkp-1 not only plays a critical role in the regulation of cytokine production but also orchestrates the bactericidal activities of the innate immune system and controls the metabolic response to stress.

Topics: Animals; Cyclooxygenase 2; Dual Specificity Phosphatase 1; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Escherichia coli Infections; Glucose; Glycogen; Gram-Negative Bacterial Infections; Hyperlipidemias; Inflammation; Interleukin-10; Interleukin-6; Lipid Metabolism; Mice; Mice, Knockout; Nitric Oxide Synthase Type II; Sepsis; Tumor Necrosis Factor-alpha

Fatty liver is commonly associated with insulin resistance and type 2 diabetes, but it is unclear whether triacylglycerol accumulation or an excess flux of lipid intermediates in the pathway of triacyglycerol synthesis are sufficient to cause insulin resistance in the absence of genetic or diet-induced obesity. To determine whether increased glycerolipid flux can, by itself, cause hepatic insulin resistance, we used an adenoviral construct to overexpress glycerol-sn-3-phosphate acyltransferase-1 (Ad-GPAT1), the committed step in de novo triacylglycerol synthesis. After 5-7 days, food intake, body weight, and fat pad weight did not differ between Ad-GPAT1 and Ad-enhanced green fluorescent protein control rats, but the chow-fed Ad-GPAT1 rats developed fatty liver, hyperlipidemia, and insulin resistance. Liver was the predominant site of insulin resistance; Ad-GPAT1 rats had 2.5-fold higher hepatic glucose output than controls during a hyperinsulinemic-euglycemic clamp. Hepatic diacylglycerol and lysophosphatidate were elevated in Ad-GPAT1 rats, suggesting a role for these lipid metabolites in the development of hepatic insulin resistance, and hepatic protein kinase Cepsilon was activated, providing a potential mechanism for insulin resistance. Ad-GPAT1-treated rats had 50% lower hepatic NF-kappaB activity and no difference in expression of tumor necrosis factor-alpha and interleukin-beta, consistent with hepatic insulin resistance in the absence of increased hepatic inflammation. Glycogen synthesis and uptake of 2-deoxyglucose were reduced in skeletal muscle, suggesting mild peripheral insulin resistance associated with a higher content of skeletal muscle triacylglycerol. These results indicate that increased flux through the pathway of hepatic de novo triacylglycerol synthesis can cause hepatic and systemic insulin resistance in the absence of obesity or a lipogenic diet.

Topics: Adenoviridae; Animals; Deoxyglucose; Fatty Liver; Gene Expression; Glycerol-3-Phosphate O-Acyltransferase; Glycogen; Hyperlipidemias; Insulin Resistance; Interleukin-1beta; Lipid Metabolism; Liver; Male; Muscle, Skeletal; NF-kappa B; Protein Kinase C-epsilon; Rats; Rats, Wistar; Transduction, Genetic; Triglycerides; Tumor Necrosis Factor-alpha

D-Glucose-6-phosphatase is a key regulator of endogenous glucose production, and its inhibition may improve glucose control in type 2 diabetes. Herein, 2'-O-(2-methoxy)ethyl-modified phosphorothioate antisense oligonucleotides (ASOs) specific to the glucose 6-phosphate transporter-1 (G6PT1) enabled reduction of hepatic D-Glu-6-phosphatase activity in diabetic ob/ob mice. Treatment with G6PT1 ASOs decreased G6PT1 expression, reduced G6PT1 activity, blunted glucagon-stimulated glucose production, and lowered plasma glucose concentration in a dose-dependent manner. In contrast to G6PT1 knock-out mice and patients with glycogen storage disease, excess hepatic and renal glycogen accumulation, hyperlipidemia, neutropenia, and elevations in plasma lactate and uric acid did not occur. In addition, hypoglycemia was not observed in animals during extended periods of fasting, and the ability of G6PT1 ASO-treated mice to recover from an exogenous insulin challenge was not impaired. Together, these results demonstrate that effective glucose lowering by G6PT1 inhibitors can be achieved without adversely affecting carbohydrate and lipid metabolism.

Topics: Acidosis, Lactic; Animals; Antiporters; Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 2; Glucagon; Glucose-6-Phosphatase; Glycogen; Glycogen Storage Disease; Hyperlipidemias; Hyperuricemia; Hypoglycemia; Kidney; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Monosaccharide Transport Proteins; Oligoribonucleotides, Antisense; RNA, Messenger

Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.

Topics: 3-Hydroxybutyric Acid; Adenoviridae; Animals; Blood Glucose; Blotting, Northern; Blotting, Western; Cholesterol; Diabetes Mellitus, Experimental; DNA-Binding Proteins; Etoposide; Gluconeogenesis; Glucose; Glycogen; Hepatocytes; Hyperglycemia; Hyperlipidemias; Insulin; Insulin Resistance; Isoxazoles; Lipids; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Statistical; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Time Factors; Transcription Factors; Triglycerides

A considerable amount of clinical and experimental evidence now exists suggesting the involvement of free radical-mediated oxidative processes in the pathogenesis of diabetic complications. If the diabetic state is associated with a generalized increase in oxidative stress, it might well be reflected in the alterations in embryonic and fetal development during pregnancy. In the present study, incidence of the malformed fetuses, biochemical parameters and antioxidant system activity of streptozotocin (STZ)-induced diabetic pregnant rats was investigated and the results obtained were compared with those of the control group (non-diabetic). Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. All the females were killed on Day 21 of pregnancy and the fetuses were analyzed. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic dams presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased reduced glutathione (GSH), hepatic glycogen and superoxide dismutase (SOD) determinations. There was an increased incidence of skeletal and visceral malformation in fetuses from diabetic rats. Our findings suggest that oxidative stress occurs in the diabetic pregnant state, which might promote maternal homeostasis alterations. These diabetic complications might be a contributory factor to conceptus damage causing embryonic death (abortion/miscarriage) or the appearance of malformations in the fetuses of diabetic dams. Antioxidant treatment of women with diabetes may be important in future attempts to prevent congenital malformations.

Topics: Animals; Antioxidants; Congenital Abnormalities; Diabetes Mellitus, Experimental; Female; Gestational Age; Glutathione; Glycogen; Hypercholesterolemia; Hyperglycemia; Hyperlipidemias; Hypertriglyceridemia; Liver; Male; Oxidative Stress; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Wistar; Superoxide Dismutase; Uric Acid

Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial pressure in hyperlipidaemic transgenic mice overexpressing apolipoprotein C1 (APOC1). Previous studies have shown that APOC1 transgenic mice develop hyperlipidaemia primarily because of an impaired hepatic uptake of very low density lipoprotein (VLDL).. Basal and hyperinsulinaemic (6 mU.kg-1.min-1), euglycaemic (7 mmol/l) clamps with 3(-)3H-glucose or 9,10(-)3H-palmitic acid infusions and in situ freeze clamped tissue collection were carried out.. The APOC1 mice showed increased basal plasma cholesterol, triglyceride, NEFA and decreased glucose concentrations compared with wild-type mice (7.0 +/- 1.2 vs 1.6 +/- 0.1, 9.1 +/- 2.3 vs 0.6 +/- 0.1, 1.9 +/- 0.2 vs 0.9 +/- 0.1 and 7.0 +/- 1.0 vs 10.0 +/- 1.1 mmol/l, respectively, p < 0.05). Basal whole body glucose clearance was increased twofold in APOC1 mice compared with wild-type mice (18 +/- 2 vs 10 +/- 1 ml.kg-1.min-1, p < 0.05). Insulin-mediated whole body glucose uptake, glycolysis (generation of 3H2O) and glucose storage increased in APOC1 mice compared with wild-type mice (339 +/- 28 vs 200 +/- 11; 183 +/- 39 vs 128 +/- 17 and 156 +/- 44 vs 72 +/- 17 mumol.kg-1.min-1, p < 0.05, respectively), corresponding with a twofold to threefold increase in skeletal muscle glycogenesis and de novo lipogenesis from 3-(3)H-glucose in skeletal muscle and adipose tissue (p < 0.05). Basal whole body NEFA clearance was decreased threefold in APOC1 mice compared with wild-type mice (98 +/- 21 vs 314 +/- 88 ml.kg-1.min-1, p < 0.05). Insulin-mediated whole body NEFA uptake, NEFA oxidation (generation of 3H2O) and NEFA storage were lower in APOC1 mice than in wild-type mice (15 +/- 3 vs 33 +/- 6; 3 +/- 2 vs 11 +/- 4 and 12 +/- 2 vs 22 +/- 4 mumol.kg-1.min-1, p < 0.05) in the face of higher plasma NEFA concentrations (1.3 +/- 0.3 vs 0.5 +/- 0.1 mmol/l, p < 0.05), respectively. Mean arterial pressure and heart rate were similar in APOC1 vs wild-type mice (82 +/- 4 vs 85 +/- 3 mm Hg and 459 +/- 14 vs 484 +/- 11 beats.min-1).. 1) Hyperlipidaemic APOC1 mice show reduced NEFA and increased glucose metabolism under both basal and insulin-mediated conditions, suggesting an intrinsic defect in NEFA metabolism. Primary hyperlipidaemia alone in APOC1 mice does not lead to insulin resistance for glucose metabolism and high blood pressure.

Topics: Animals; Apolipoprotein C-I; Apolipoproteins C; Blood Glucose; Blood Pressure; Cholesterol; Fatty Acids, Nonesterified; Gene Expression; Glucose; Glucose Clamp Technique; Glycogen; Humans; Hyperlipidemias; Insulin; Lipid Metabolism; Liver; Mice; Mice, Transgenic; Muscle, Skeletal; Palmitic Acid; Triglycerides; Tritium

This study was designed to determine changes in myocardial contractile function and fuel selection during moderate coronary hypoperfusion in the presence of elevated plasma free fatty acid (FFA) at normal and reduced blood glucose concentrations. Coronary perfusion pressure (CPP) was sequentially lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs. Regional glucose uptake (GU), fatty acid uptake (FAU), percentage segment shortening (%SS), and oxygen consumption (MV O(2)) were determined with normal arterial plasma FFA concentrations (Group 1) or with elevated FFA concentrations (Groups 2 and 3). In Group 3, glucose in the coronary perfusate blood was reduced from 3.53+/-0.36 to 0.15+/-0.03 m M by hemodialysis. In Group 1, FAU fell by 85% as CPP was lowered to 60 mmHg and remained depressed as CPP was reduced further; GU did not fall significantly. Hyperlipidemia in Group 2 did not alter GU at any CPP, but maintained FAU at baseline levels until CPP was lowered to 40 mmHg. At 40 mmHg CPP, myocardial function and metabolic variables were similar in Groups 1 and 2. In Group 3 at 40 mmHg, FAU increased four-fold and MV O(2)doubled v Groups 1 and 2, and GU fell to zero. Despite these metabolic changes, %SS in Group 3 was unchanged relative to Group 2. Addition of glucose to the dialysate prevented the effects of dialysis on FAU, GU, and MV O(2). Thus, preferential glucose oxidation sustains myocardial oxygen utilization efficiency [(heart rate x %SS x maximum left ventricular pressure)/MV O(2)] during hypoperfusion. Blocking preferential glucose oxidation by combined hyperlipidemia and hypoglycemia lowers oxygen utilization efficiency, but does not compromise myocardial contractile function.

Topics: Animals; Blood Glucose; Dogs; Fatty Acids; Female; Glucose; Glycogen; Hemodynamics; Hyperlipidemias; Hypoglycemia; Ischemia; Lactic Acid; Male; Myocardial Contraction; Myocardium; Oxygen; Oxygen Consumption; Perfusion; Pressure

To examine the effect of increased hexosamine flux in liver, the rate-limiting enzyme in hexosamine biosynthesis (glutamine:fructose-6-phosphate amidotransferase [GFA]) was overexpressed in transgenic mice using the PEPCK promoter. Liver from random-fed transgenic mice had 1.6-fold higher GFA activity compared with nontransgenic control littermates (276 +/- 24 pmol x mg(-1) x min(-1) in transgenic mice vs. 176 +/- 18 pmol x mg(-1) x min(-1) in controls, P < 0.05) and higher levels of the hexosamine end product UDP-N-acetyl glucosamine (288 +/- 11 pmol/g in transgenic mice vs. 233 +/- 10 pmol/g in controls, P < 0.001). Younger transgenic mice compared with control mice had lower fasting serum glucose (4.8 +/- 0.5 mmol/l in transgenic mice vs. 6.5 +/- 0.8 mmol/l in controls, P < 0.05) without higher insulin levels (48.0 +/- 7.8 pmol/l in transgenic mice vs. 56.4 +/- 5.4 pmol/l in controls, P = NS); insulin levels were significantly lower in transgenic males (P < 0.05). At 6 months of age, transgenic animals had normal insulin sensitivity by the hyperinsulinemic clamp technique. Hepatic glycogen content was higher in the transgenic mice (108.6 +/- 5.2 pmol/g in transgenic mice vs. 32.8 +/- 1.3 micromol/g in controls, P < 0.01), associated with an inappropriate activation of glycogen synthase. Serum levels of free fatty acids (FFAs) and triglycerides were also elevated (FFAs, 0.67 +/- 0.03 mmol/l in transgenic mice vs. 0.14 +/- 0.01 in controls; triglycerides, 1.34 +/- 0.15 mmol/l in transgenic mice vs. 0.38 +/- 0.01 in controls, P < 0.01). Older transgenic mice became heavier than control mice and exhibited relative glucose intolerance and insulin resistance. The glucose disposal rate at 8 months of age was 154 +/- 5 mg x kg(-1) x min(-1) in transgenic mice vs. 191 +/- 6 mg x kg(-1) x min(-1) in controls (P < 0.05). We conclude that hexosamines are mediators of glucose sensing for the regulation of hepatic glycogen and lipid metabolism. Increased hexosamine flux in the liver signals a shift toward fuel storage, resulting ultimately in obesity and insulin resistance.

Topics: Adenosine Triphosphate; Animals; Fatty Acids, Nonesterified; Glucosamine; Glucose Intolerance; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); Glycogen; Glycogen Synthase; Hyperlipidemias; Liver; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Phosphoenolpyruvate Carboxykinase (GTP); Phosphorylases; Reference Values; Triglycerides; Uridine Diphosphate N-Acetylgalactosamine

Type 2 diabetes mellitus and obesity are characterized by fasting hyperinsulinemia, insulin resistance with respect to glucose metabolism, elevated plasma free fatty acid (FFA) levels, hypertriglyceridemia, and decreased high-density lipoprotein (HDL) cholesterol. An association between hyperinsulinemia and dyslipidemia has been suggested, but the causality of the relationship remains uncertain. Therefore, we infused eight 12-week-old male catheterized conscious normal rats with insulin (1 mU/min) for 7 days while maintaining euglycemia using a modification of the glucose clamp technique. Control rats (n = 8) received vehicle infusion. Baseline FFAs were 1.07+/-0.13 mmol/L, decreased to 0.57+/-0.10 (P < .05) upon initiation of the insulin infusion, and gradually increased to 0.95+/-0.12 by day 7 (P = NS vbaseline). On day 7 after a 6-hour fast, plasma insulin, glucose, and FFA levels in control and chronically hyperinsulinemic rats were 32+/-5 versus 116+/-21 mU/L (P < .005), 122+/-4 versus 129+/-8 mg/dL (P = NS), and 1.13+/-0.18 versus 0.95+/-0.12 mmol/L (P = NS); total plasma triglyceride and cholesterol levels were 78+/-7 versus 66+/-9 mg/dL (P = NS) and 50+/-3 versus 47+/-2 mg/dL (P = NS), respectively. Very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and HDL2 and HDL3 subfractions of plasma triglyceride and cholesterol were similar in control and hyperinsulinemic rats. Plasma FFA correlated positively with total (r = .61, P < .005) triglycerides. On day 7 after an 8-hour fast, hyperinsulinemic-euglycemic clamps with 3-3H-glucose infusion were performed in all rats. Chronically hyperinsulinemic rats showed peripheral insulin resistance (glucose uptake, 15.8+/-0.8 v 19.3+/-1.4 mg/kg x min, P < .02) but normal suppression of hepatic glucose production (HGP) compared with control rats (4.3+/-1.0 v 5.6+/-1.4 mg/kg x min, P = NS). De novo tissue lipogenesis (3-3H-glucose incorporation into lipids) was increased in chronically hyperinsulinemic versus control rats (0.90+/-0.10 v 0.44+/-0.08 mg/kg x min, P < .005). In conclusion, chronic physiologic hyperinsulinemia (1) causes insulin resistance with regard to the suppression of plasma FFA levels and increases lipogenesis; (2) induces peripheral but not hepatic insulin resistance with respect to glucose metabolism; and (3) does not cause an elevation in VLDL-triglyceride or a reduction in HDL-cholesterol.

Topics: Animals; Blood Glucose; Chronic Disease; Energy Metabolism; Fatty Acids, Nonesterified; Glucose Clamp Technique; Glycogen; Glycolysis; Hyperinsulinism; Hyperlipidemias; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Lipoproteins; Liver; Male; Rats; Rats, Sprague-Dawley; Triglycerides

To investigate the mechanism by which free fatty acids (FFA) affect glucose uptake, we studied the effect of chronic elevation (24 h) of plasma FFA in rats on whole body glucose disposal and glucose utilization index (GUI) in the basal state and under a euglycemic hyperinsulinemic clamp in relation to the amount of insulin-responsive glucose transporter (IRGT, i.e., GLUTU) protein in different muscles (oxidative and glycolytic) and adipose tissue. Infusion of intralipid in the basal state led to a approximately 40% increase in whole body glucose uptake and a approximately 250% increase in GUI in adipose tissue as compared to control rats. There was no change in the amount of IRGT protein in any of the muscle types whereas in fat depots it was either unchanged or decreased. Under moderate of supraphysiological hyperinsulinemia, increment of whole body glucose disposal was significantly lower in intralipid perfused rats when compared to controls (approximately 110 microU/mL: 0.7 +/- 0.1 vs. 1.3 +/- 0.1 mg/min, P < 0.02; approximately 1000 microU/mL: 3.0 +/- 0.2 vs. 3.9 +/- 0.4 mg/min, P < 0.02). Under moderate hyperinsulinemia stimulation, GUI was significantly reduced in different muscles and adipose tissue as compared to controls. We conclude that peripheral insulin resistance which occurs after elevation of plasma FFA levels does not seem to be explained by changes in the amount of IRGT protein in either oxidative or glycolytic skeletal muscle. Thus fatty acid infusion appears to be associated with a defect in IRGT translocation to the plasma membrane, fusion with the membrane, or intrinsic activity.

Topics: Adipose Tissue; Animals; Biological Transport, Active; Blood Glucose; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Glucose; Glucose Transporter Type 4; Glycogen; Glycolysis; Hyperlipidemias; Infusions, Intravenous; Insulin; Insulin Resistance; Kinetics; Liver Glycogen; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Rats; Rats, Wistar

Several investigators have reported that feeding a semi-synthetic diet of casein and dextrose to New Zealand White (NZW) rabbits will increase total serum cholesterol concentration, principally through an increase in the beta-lipoprotein fractions, thereby creating a useful model for atherosclerosis research. Although there is evidence to suggest that the dextrose/casein diet alters low-density lipoprotein receptor and bile acid clearance of cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiology of the rabbit have received little attention. In this study feeding a diet of casein and dextrose of male NZW rabbits for 4 weeks resulted in changes in the serum lipid concentrations. During that time the rabbits fed the dextrose/casein diet gained less weight than did control rabbits. In the test diet rabbits, liver aspartate and alanine transaminase activities were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end of the reference range. Necropsy findings included hepatomegaly caused by vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement of the liver cells was due to glycogen deposition. Adrenal glands from animals fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction of the cytoplasm. In a second study the level of dietary fiber was doubled. This resulted in a three-fold increase in lipid concentrations, compared with the fivefold increase in the first study. The liver enzyme activities were increased to the same extent as in the first study. Histologic changes were comparable to those in the first study. The activity of hepatic cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4 pmol/min/mg of protein, compared with the control value of 7.7 +/- 1.1 pmol/min/mg of protein (P < 0.05) in the second study. The improved rate of weight gain and the lesser increase in total serum cholesterol concentration in the second study with increased dietary fiber suggest that two separate activities may be involved. Although the level of dietary fiber may be related to weight gain and total serum cholesterol values, the relation to the decrease in liver transaminase activities in study 1 was probably coincidental. It appears tha

Topics: Adrenal Glands; Animals; Brain; Caseins; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet; Disease Models, Animal; Food, Formulated; Glucose; Glycogen; Hydroxymethylglutaryl CoA Reductases; Hyperlipidemias; Lipoproteins; Liver; Male; Microscopy, Electron; Organ Size; Rabbits

Monosodium glutamate (MSG) was administered subcutaneously to adult male mice for 6 days at dose levels of 2, 4, and 8 mg/g body wt. Dose levels above 4 mg/g body wt. showed significant increase in content of liver total lipids, phospholipids, triglycerides and free fatty acids, 31 days after the last injection. Blood glutamate level was significantly increased in all the groups but blood glutamine was increased in 4 and 8 mg/g body wt. groups (Groups III and IV) only. Blood pyruvate and glucose was significantly increased whereas liver glycogen and blood lactate was decreased in group III and IV. Activity of lactate dehydrogenase was significantly reduced both in serum and liver but the activity of glucose-6-phosphate dehydrogenase was significantly increased in RBC and liver at dose levels of 4 and 8 mg/g body wt. All these observations are suggestive of the fact that carbohydrate metabolism is shifted towards lipogenesis and hence leads to hyperlipidemia.

Topics: Animals; Carbohydrate Metabolism; Carbohydrates; Cholesterol; Glucosephosphate Dehydrogenase; Glutamates; Glutamine; Glycogen; Hyperlipidemias; L-Lactate Dehydrogenase; Lactates; Lipid Metabolism; Lipids; Liver; Male; Mice; Pyruvates; Sodium Glutamate

The effects of reduced dietary fat intake on plasma lipid levels were examined in diabetic rats. One week after induction of diabetes (D) with streptozotocin (65 mg/kg, iv), the animals were fed food pellets consisting of 1.5% (D1.5), 2.5% (D2.5) or 5% (D5) fat for two weeks. Irrespective of the diets, both food and water consumed by untreated diabetic rats were 2- to 5-fold greater respectively compared to normal. Plasma glucose concentrations were also similarly increased. Plasma and skeletal muscle lipid levels were significantly greater than controls in D2.5 and D5, but not in the D1.5 group. Plasma and muscle lipid concentrations correlated directly with fat consumption. In D5 rats receiving insulin treatment, plasma glucose and lipid concentrations were comparable to control values. These findings indicate that the degree of hyperlipidemia in chronically diabetic rats is directly related to dietary fat intake. They also demonstrate that dietary interventions can modulate some of the metabolic abnormalities in diabetes.

Topics: Analysis of Variance; Animals; Diabetes Mellitus, Experimental; Dietary Fats; Glycogen; Hyperlipidemias; Lipid Metabolism; Lipids; Male; Muscles; Myocardium; Rats; Rats, Inbred Strains; Triglycerides

A TRH fixation in vitro occurs at the level of the human polynuclear neutrophil, which suggests putative membrane receptor (s) for the hypothalamic hormone. After TRH administration, enzyme modifications (myeloperoxydase, alkaline phosphatase) and metabolism changes (PAS, Sudan black) happen in vivo within the neutrophil, showing a functional activation of that blood cell. Two processes may be considered to explain those data: 1) the TRH is directly fixed, as observed in vitro; 2) a mediate hormone (TSH, T4, T3) is released capable of binding the granulocyte membrane.

Topics: Alkaline Phosphatase; Glycogen; Histocytochemistry; Humans; Hyperlipidemias; In Vitro Techniques; Neutrophils; Peroxidase; Peroxidases; Thyrotropin-Releasing Hormone

Topics: Animals; Clofibrate; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Hyperlipidemias; Lipoproteins, VLDL; Liver; Lysosomes; Male; Microbodies; Microscopy, Electron; Mitochondria, Liver; Models, Biological; Rats; Sucrose; Triglycerides

Topics: Adipose Tissue; Adult; Blood Glucose; Cholesterol; Fatty Acids; Female; Fructose; Glycerol; Glycogen; Humans; Hyperlipidemias; Insulin; Lipoproteins, VLDL; Liver; Male; Middle Aged; Phospholipids; Sucrose; Triglycerides

Topics: Animals; Arteries; Arteriosclerosis; Blood Glucose; Cholesterol; Diet, Atherogenic; Fatty Acids, Nonesterified; Fatty Liver; Glycogen; Hyperlipidemias; Intestinal Absorption; Lipoproteins; Liver; Male; Metformin; Phenformin; Phospholipids; Rabbits

Topics: Adipose Tissue; Body Weight; Cholesterol; Electrophoresis, Paper; Fasting; Glycogen; Humans; Hyperlipidemias; Lipid Metabolism; Lipoproteins; Lipoproteins, LDL; Male; Muscles; Nicotinic Acids; Time Factors; Triglycerides; Ultracentrifugation

Topics: Administration, Oral; Adult; Aged; Alanine Transaminase; Aspartate Aminotransferases; Blood Glucose; Clofibrate; Fatty Liver; Glycogen; Humans; Hyperlipidemias; Lipids; Liver; Long-Term Care; Middle Aged; Triglycerides

Topics: Adipose Tissue; Animals; Carbon Isotopes; Diaphragm; Diet; Fatty Acids; Glucose; Glycogen; Hyperlipidemias; Hypothalamus; Lipid Metabolism; Liver; Male; Obesity; Rats

Topics: Biopsy; Child, Preschool; Epinephrine; Fasting; Fats; Follow-Up Studies; Glucagon; Glucose; Glucosidases; Glycogen; Glycogen Storage Disease; Humans; Hypercholesterolemia; Hyperlipidemias; Infant; Male

Topics: Animals; Dietary Carbohydrates; Dietary Fats; Estrogens; Female; Fructose; Glucose; Glycogen; Humans; Hyperlipidemias; Intestinal Absorption; Lipid Metabolism; Liver; Male; Maltose; Menopause; Middle Aged; Nutritional Physiological Phenomena; Papio; Rabbits; Rats; Sex Factors; Starch; Sucrose; Triglycerides

Topics: Antihypertensive Agents; Child; Diazoxide; Drug Eruptions; Drug Hypersensitivity; Glucose Tolerance Test; Glycerides; Glycogen; Glycogen Storage Disease Type I; Humans; Hyperglycemia; Hyperlipidemias; Hypoglycemia; Insulin; Lipids; Male; Triglycerides; Xanthomatosis

Topics: Adrenocorticotropic Hormone; Animals; Fatty Acids; Glycogen; Growth Hormone; Haplorhini; Hyperglycemia; Hyperlipidemias; Hypophysectomy; Muscles; Placental Extracts; Proteins; Rabbits; Rats; Triglycerides

Topics: Adipose Tissue; Fasting; Fatty Acids; Glycerides; Glycogen; Hyperlipidemias; Lipid Metabolism; Lipoprotein Lipase; Lipoproteins; Metabolism; Nephrotic Syndrome; Rats; Research