glycogen and Uremia

Topics: Carbohydrate Metabolism; Glucose; Glycogen; Humans; Hypertension; Neutrophils; Oxidation-Reduction; Renal Dialysis; Uremia

Chronic hemodialysis (HD) may lead to losses of carnitine from plasma and muscle. Plasma carnitine does not reflect the body content of carnitine. The purpose of this study was the evaluation of total and free plasma and muscle carnitine concentrations (TPC, FPC, TMC, FMC), muscle glycogen and the relationship between plasma and tissue carnitine content and the basic indices of lipid metabolism in HD patients. The studies were conducted in two groups: the first one consisted of 37 HD patients (19 F, 18 M), the second one served as the control and was composed of 29 (10 F, 19 M) patients with healthy kidneys. Tissue specimens in HD patients were taken during surgery on arterio-venous fistula from brachioradial muscle. Carnitine and glycogen measurements were performed using enzymatic methods according to Cederblad and Huijng respectively. Total cholesterol (CH), HDL-CH, and triglycerides were assayed by enzymatic commercial test system (Boehringer-Mannheim, Germany). To summarise, we found the following phenomena in our HD patients in comparison with the controls: 1) In plasma: similar TPC but decreased FPC levels and FPC/TPC ratio which may suggest free carnitine deficiency. 2) In muscle: significantly lower TMC and FMC levels but normal FMC/ITMC ratio. 3) Negative correlation between TMC and FMC levels and duration of dialysis treatment. 4) No correlation between plasma and muscle camitine concentration. 5) Significantly higher concentration of muscle glycogen which could be explained by the changes in the structure of muscle fibres in HD patients and/or lower physical activity. 6) A positive correlation between FPC/APC or FPC/TPC ratio and HDL-CH in HD patients which may suggest that an appropriate proportion between free and acylcarnitines may influence HDL-CH levels in that population.

Topics: Adult; Aged; Body Composition; Carnitine; Case-Control Studies; Female; Glycogen; Humans; Lipid Metabolism; Male; Middle Aged; Muscle, Skeletal; Renal Dialysis; Statistics, Nonparametric; Uremia

Insulin-mediated glucose metabolism was examined in vivo and in vitro in a chronically uremic (4-week) rat model established by a 90% nephrectomy. Using the euglycemic insulin clamp technique, uremic rats demonstrated a 28% reduction (P less than .01) in total body glucose disposal compared with pair-fed controls. Suppression of hepatic glucose production by insulin was not impaired. The ability of insulin to promote glycogen synthesis by the soleus muscle in vitro was normal in uremic rats. In contrast, the ability of insulin to enhance both glycolysis and glucose oxidation by the soleus muscle was significantly reduced (P less than .01) in uremic rats. These results provide evidence that at least two intracellular metabolic defects, ie, in the glycolytic and glucose oxidative pathways, contribute to the insulin resistance of chronic uremia.

Topics: Animals; Glucose; Glycogen; Glycolysis; Insulin; Insulin Resistance; Liver; Male; Muscles; Oxidation-Reduction; Rats; Rats, Inbred Strains; Uremia

Insulin resistance has been demonstrated in chronic renal failure patients and may be improved by exercise training, but the mechanisms have not been identified. In this study, the response of glucose uptake, glycogen synthesis, and glucose utilization via glycolysis (glycolytic utilization) to stimulation by insulin and/or acute exercise were determined in isolated muscles from rats with moderate renal insufficiency that were exercise trained or remained sedentary. Moderate renal insufficiency had no effect on the basal rate, insulin sensitivity, or insulin responsiveness of glucose uptake, glycogen synthesis, or glycolytic utilization in muscle. The enhanced insulin responsiveness of both glycogen synthesis and glucose uptake following acute exercise, noted in control animals, was less in rats with moderate renal insufficiency, but the enhanced basal rate and insulin sensitivity after exercise were unaffected by moderate renal insufficiency. Exercise training increased the insulin sensitivity and responsiveness of muscle glucose uptake and glycolytic utilization in rats with moderate renal insufficiency and in controls. The effects of acute exercise and exercise training on insulin responsiveness of glucose uptake were additive in controls but not in animals with moderate renal insufficiency. These findings are compatible with the concept that moderate renal insufficiency is associated with a postreceptor defect in insulin's action in muscle, detectable only following maximal stimulation of glucose transport by insulin and exercise, and partially correctable by exercise training.

Topics: Animals; Blood Urea Nitrogen; Creatinine; Female; Glucose; Glycogen; Glycolysis; Insulin; Kinetics; Muscles; Physical Exertion; Rats; Rats, Inbred Strains; Rest; Uremia

In order to evaluate the potential role of hyperkalemia and metabolic acidosis on the disturbances of carbohydrate metabolism normally seen in uremia, a specific model of acute uremia devoid of hyperkalemia and severe metabolic acidosis was chosen. Therefore, rats were deprived of potassium prior to induction of acute uremia. Potassium depletion caused a significant decrease of muscle and liver glycogen due to activation of phosphorylase kinase, whereas glycogen concentration in heart muscle was unchanged and elevated in the kidney of sham-operated and ureter-ligated animals. In contrast, glucose concentrations were enhanced in the liver and the kidney, unchanged in heart muscle and decreased in skeletal muscle. We conclude that carbohydrate abnormalities occur in acute uremia despite normokalemia and mild metabolic acidosis. Furthermore, acute uremia accompanied by prior potassium depletion results in no net effect on cardiac glycogen metabolism but stimulates glycogenolysis in both skeletal muscle and the liver.

Topics: Animals; Glucose; Glycogen; Kidney; Liver; Liver Glycogen; Male; Muscles; Potassium; Potassium Deficiency; Rats; Rats, Inbred Strains; Uremia

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Catecholamines; Creatinine; Glucagon; Gluconeogenesis; Glucose Tolerance Test; Glycogen; Humans; Insulin; Liver; Mitochondria, Liver; Rats; Renal Dialysis; Uremia

The mechanisms underlying the abnormal insulin-mediated muscle glucose metabolism occurring in acute uremia (ARF) have not been identified. To characterize the defects, insulin dose-response curves for glucose uptake, glycogen synthesis, glucose oxidation, glycolysis, and lactate release were measured in incubated rat epitrochlearis muscles. ARF did not affect insulin sensitivity, but decreased the responsiveness to insulin of glucose uptake, glycogen synthesis, and glucose oxidation. Glycogen synthesis was subnormal at all levels of insulin and at the maximal insulin concentration; it was 54% lower in muscles of ARF compared to control rats. This inhibition of glycogen synthesis in ARF could be caused by a 23% decrease in the total activity of muscle glycogen synthase and the percentage of enzyme in the activated form. Glycogen phosphorylase activity was unchanged by ARF. ARF also increased the ratio of muscle lactate release to glucose uptake at concentrations of insulin from 10 to 10(4) microU/ml. In the absence and presence of insulin, muscle protein degradation was increased by ARF. In individual muscles incubated with insulin, the rate of proteolysis was correlated with the ratio of lactate release to glucose uptake (r = + 0.82; P less than 0.01). From the insulin dose-response relationships and changes in enzyme activities, we conclude that ARF increases protein degradation in muscle and causes abnormal insulin-mediated glucose metabolism. The abnormalities in glucose metabolism are caused by changes in post-receptor events.

Topics: Animals; Biological Transport, Active; Glucose; Glycogen; Insulin; Insulin Resistance; Lactates; Lactic Acid; Male; Muscles; Proteins; Rats; Rats, Inbred Strains; Uremia

The effects of exercise training on muscle protein catabolism in uremia were studied in female rats. Rats made uremic by 3/4 nephrectomy were compared with sham-operated control female rats under conditions of exercise training by swimming or no exercise. The release of amino acids from epitrochlearis muscle in vitro was measured. Body weight epitrochlearis muscle weight, and epitrochlearis protein content were similar among groups. Uremia increased the release of phenylalanine and tyrosine 33% and alanine 50% from muscle of sedentary rats. Citrate synthase activity and glycogen content of muscle were increased twofold by exercise in both controls and uremics. Exercise increased the release of alanine (60%), glutamine (50%), and pyruvate (30%) from muscles of control rats, but it decreased to control levels the release of phenylalanine and tyrosine in uremic rats. Alanine release remained elevated. To determine if exercise training increases in vitro muscle sensitivity to insulin, we incubated muscle with and without 0.01 U/ml of insulin. Phenylalanine and tyrosine release was reduced minimally by insulin in both sedentary uremic and control groups. Glucose uptake was enhanced by 55% in both groups. But in the exercised uremic and control groups, insulin reduced phenylalanine and tyrosine release by 50% and increased glucose uptake by 75%. These results suggest that exercise training reduces muscle protein catabolism in uremia; and this reduction is associated with enhanced muscle response to pharmacologic doses of insulin in control and uremic rats.

Topics: Amino Acids; Animals; Blood Urea Nitrogen; Calcium; Citrate (si)-Synthase; Creatinine; Female; Glucose; Glycogen; In Vitro Techniques; Insulin; Lactates; Muscle Proteins; Muscles; Phosphates; Physical Exertion; Pyruvates; Rats; Rats, Inbred Strains; Swimming; Swine; Uremia

Isolated hindquarters of bilaterally nephrectomized and sham-operated rats were perfused in the presence and absence of 14C-labelled serine, respectively. After a perfusion period of 30 min 14C-serine was 4,074 +/- 270 dpm/ml in the perfusion medium of sham-operated animals and decreased to 2,800 +/- 190 dpm/ml in the medium of acutely uraemic rats. Muscle glycogen concentration in sham-operated animals was 1.10 +/- 0.04 mg/g wet weight in the absence and 1.03 +/- 0.11 mg/g in the presence of serine. In contrast, in acutely uraemic rats there was a glycogen concentration of 0.57 +/- 0.09 mg/g in the absence of serine. Glycogen was increased in the presence of serine in the perfusion medium, the value being 1.50 +/- 0.13 mg glycogen/g wet weight. Incorporation of labelled serine into skeletal muscle glycogen was significantly higher in acutely uraemic animals (15 +/- 0.5 mumol/g glycogen) than in sham-operated animals (10 +/- 0.4 mumol/g). The results are compatible with the hypothesis that serine increases muscle glycogen synthesis in acute uraemia.

Topics: Acute Disease; Animals; Female; Glycogen; Hindlimb; Muscles; Perfusion; Rats; Rats, Inbred Strains; Serine; Uremia

Carbohydrate metabolism in salivary glands of acutely uremic rats was investigated. In the submandibular glands there was an increase of total carbohydrate and glycogen content 24 and 48 h following binephrectomy or ureter ligation. In contrast, lactate concentration was significantly lower. Similar alterations of carbohydrate metabolism could not be observed in sublingual or parotid glands of acutely uremic rats.

Topics: Acute Disease; Animals; Carbohydrate Metabolism; Female; Glucose; Glycogen; Lactates; Parotid Gland; Rats; Rats, Inbred Strains; Salivary Glands; Sublingual Gland; Submandibular Gland; Uremia

This report describes qualitative and quantitative studies performed on ten muscle biopsies from chronic uremic patients on renal dialysis at light and electron microscopic (EM) levels. The muscle biopsies showed myopathic changes (variation in fiber size, central nuclei, and fiber splitting). Histochemical studies showed type II fiber atrophy and lipid deposits. The ultrastructural study showed disruption of myofibrillary architecture and subsarcolemmal deposits of glycogen, mitochondria, and lipids. Quantitative estimations of the subcellular organelles revealed a statistically significant increase in lipid and glycogen contents of the muscle. The myopathic changes, type II atrophy, and lipid and glycogen deposits in chronic uremic patients raise the question of the effects of uremia and/or chronic dialysis on muscle metabolism.

Topics: Adult; Aged; Biopsy; Female; Glycogen; Humans; Lipids; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscles; Organoids; Renal Dialysis; Time Factors; Uremia

Topics: Acute Disease; Animals; Diet; Female; Glycogen; Glycogen Synthase; Phosphorylases; Protein Binding; Proteins; Rats; Rats, Inbred Strains; Serine; Uremia

Topics: Acute Disease; Animals; Dietary Proteins; Enzyme Activation; Fasting; Glycogen; Glycogen Synthase; Insulin Resistance; Kinetics; Lactates; Muscles; Nephrectomy; Phosphorylases; Rats; Serine; Uremia

Binephrectomized rats treated with high doses of ketoleucine (0.5 g/rat per 20 hr) expired after about 45 hr. In contrast, survival time was 100% 60 hr after ureteral ligation. In comparison to animals receiving low-protein diets, addition of leucine to the diet almost doubled muscle and liver protein content whereas ketoleucine increased liver protein during the first 40 hr after operation about 1.5-fold. Skeletal muscle protein content was enhanced in the ureter-ligated rats with administration of ketoleucine. There was also about a 10-fold elevation in liver glycogen and total carbohydrate content between the 20th and 60th hr in binephrectomized rats fed leucine at 5-hr intervals. In skeletal muscle glycogen, there were no significant differences among the acutely uremic rats fed at 10-hr intervals low-protein diets alone or supplemented with leucine or ketoleucine. Leucine inhibits glycogenolysis by lowering phosphorylase alpha activity in muscle and liver, whereas ketoleucine enhances glycogenolysis in acute uremia. In rats supplemented with letoleucine, there is a progressive inactivation of glycogen synthetase I which occurs in parallel with increasing phosphorylase alpha activity. In binephrectomized rats receiving leucine supplements at 5-hr feeding intervals, the activity of liver glycogen synthetase I increases up to a maximum of 90% of total enzyme activity.

Topics: Acute Disease; Animals; Dietary Proteins; Female; Glycogen; Glycogen Synthase; Keto Acids; Kinetics; Leucine; Liver; Muscles; Phosphorylase a; Proteins; Rats; Uremia

Disturbances of carbohydrate metabolism during acute uraemia are characterized by the degradation of liver and muscle glycogen with a simultaneous activation of hepatic gluconeogenesis. After binephrectomy, the substitution of essential amino acids and keto analogues stimulate liver, but not skeletal muscle glycogen synthesis. Serine proves to be an optimal substrate for liver gluconeogenesis and muscle glycogen generation under acute uraemic conditions. Propranolol does not influence glycogenolysis of skeletal muscle in acutely uraemic rats. During starvation, acute uraemia leads to an increase of total carbohydrate content as well as of glycogen and glucose concentrations in heart muscle Alterations in carbohydrate contents are not observed in the kidney after ureter ligation. Enhanced glycogenolysis of skeletal muscle and liver during acute uraemia may be due to activation of phosphorylase kinase caused by the increased serum concentrations of various hormones (glucagon, catecholamines, parathormone) as well as free proteolytic activity, an increase of intracellular Ca2+-concentration and finally by alterations in the structure of contractile proteins.

Topics: Blood Glucose; Carbohydrate Metabolism; Gluconeogenesis; Glycogen; Hormones; Humans; Uremia

Examination of kidneys of ten patients with uremia and severe hypertension treated by chronic intermittent hemodialysis revealed a deposition of glycogen within interstitial cells of the renal medulla. This is unlike any described renal distribution of glycogen. Electron microscopic studies performed in one case demonstrated monoparticulate glycogen both diffuse in the interstitial cell cytoplasm and locally aggregated beside lipid droplets. The findings provide evidence for a metabolic abnormality of renal medullary interstitial cells in patients who have protracted uremia.

Topics: Adult; Female; Glycogen; Humans; Hypertension, Renal; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Medulla; Male; Middle Aged; Uremia

Topics: Actomyosin; Adenosine Triphosphatases; Animals; Glycogen; Muscles; Nephrectomy; Phosphorylases; Protein Kinases; Rats; Troponin; Uremia

Long term maintenance of male rats of Long Evans variety following mercuric chloride induced uremia has shown an altered intramolecular structure of muscle glycogen with no significant difference in muscle glycogen content. The structure of muscle glycogen in these uremic rats when compared to sham control rats differed significantly from the structure of liver glycogen observed earlier in nephrectomized rats (Mannan et al., 1975). Biochemical analysis of muscle glycogen revealed a significant inverse relationship between the muscle and liver glycogen structure in terms of number of segments and number of non-reducing ends. Thus, an abnormal or altered muscle glycogen intramolecular structure of uremic rats is compatible with the observation of hypoglycemic state. Attributions of this to defects in glycogenolysis due to altered configuration in intramolecular structure of glycogen molecule are discussed.

Topics: Animals; Glycogen; Liver Glycogen; Male; Mercury; Muscles; Rats; Uremia

Topics: Animals; Energy Metabolism; Fructosephosphates; Glucose; Glycogen; Insulin; Lactates; Male; Myocardium; Oxygen Consumption; Perfusion; Phosphofructokinase-1; Rats; Uremia

Topics: Animals; Arginine; Aspartic Acid; Dogs; Glucagon; Glycogen; Guanidines; Insulin; Insulin Secretion; Liver; Pancreas; Rats; Urea; Uremia

The sub-totally nephrectomized chronically uremic rat has been found to have significantly increased hepatic glucose-6-phosphate dehydrogenase activity and increased lipogenesis and glycoportein synthesis. Increased conversion of 14-C-D-glucose to 14-CO2, and increased plasma free fatty acid levels were also observed. The metabolic significance of these findings has been discussed, particularly with respect to the importance of the pentose shunt in this model. The influence of reduced diet intake, resulting from uremic anorexia, has been considered in light of changes observed. It is concluded that decreased food intake alone is unlikely to be responsible for the altered glucose utilization evident in this model.

Topics: Adipose Tissue; Animals; Fatty Acids, Nonesterified; Glucose; Glucosephosphate Dehydrogenase; Glycogen; Glycoproteins; Kidney; Lipid Metabolism; Liver; Male; Muscles; Nephrectomy; Rats; Uremia

Topics: Acute Disease; Animals; Chronic Disease; Glycogen; Hexokinase; Insulin; Myocardium; Perfusion; Rats; Uremia

Topics: Adenylyl Cyclases; Animals; Blood Glucose; Carbon Radioisotopes; Diet; Disease Models, Animal; Epinephrine; Fasting; Fatty Acids, Nonesterified; Glycogen; Glycogen Synthase; Glycolysis; Heart Rate; Insulin; Lactates; Male; Myocardium; Nephrectomy; Perfusion; Phosphoric Diester Hydrolases; Phosphorylases; Rats; Transferases; Uremia

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: Animals; Blood Pressure; Glycogen; Heart; Heart Function Tests; Male; Myocardium; Nephrectomy; Oxygen Consumption; Perfusion; Potassium; Rats; Sodium; Urea; Uremia

Topics: Animals; Chronic Disease; Glycogen; Golgi Apparatus; Kidney Failure, Chronic; Liver; Lysosomes; Mitochondria, Liver; Mitochondrial Swelling; Oxidative Phosphorylation; Rats; Urea; Uremia

Topics: Animals; Calcinosis; Cardiomyopathies; Disease Models, Animal; Endoplasmic Reticulum; Female; Glycogen; Histocytochemistry; L-Lactate Dehydrogenase; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Necrosis; Nephrectomy; Parathyroid Glands; Rats; Succinate Dehydrogenase; Transferases; Uremia

Topics: Adult; Alkaline Phosphatase; Bone Diseases; Calcium; Cytoplasm; Endoplasmic Reticulum; Female; Glomerular Filtration Rate; Glycogen; Golgi Apparatus; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Mitochondria; Organ Size; Parathyroid Glands; Phosphates; Uremia

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Biopsy; Creatinine; Female; Glycogen; Humans; Kidney Failure, Chronic; Leg; Male; Middle Aged; Muscles; Peritoneal Dialysis; Postoperative Complications; Uremia

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: Acid Phosphatase; Alkaline Phosphatase; Animals; Chlorides; Electron Transport Complex IV; Esterases; Female; Glucose-6-Phosphatase; Glucuronidase; Glycogen; Histocytochemistry; Hypertension; Methacholine Compounds; Microscopy, Electron; Monoamine Oxidase; Potassium; Rats; Sodium; Succinate Dehydrogenase; Sweat Glands; Sweating; Uremia

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

Topics: Animals; Blood; Diaphragm; Glucose; Glycogen; Ketoglutaric Acids; Lactates; Muscles; Oxygen Consumption; Rats; Uremia

Topics: Adolescent; Adult; Aged; Biopsy; Chlorides; Chronic Disease; Female; Glycogen; Histocytochemistry; Humans; Magnesium; Male; Middle Aged; Muscles; Phosphorus; Potassium; Sodium; Uremia; Water-Electrolyte Balance