glycogen and Kidney-Failure--Chronic

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glucose; Glycogen; Homeostasis; Humans; Hypoglycemia; Insulin Resistance; Kidney; Kidney Failure, Chronic; Lactates; Lactic Acid; Male

Chronic renal insufficiency (CRI) is often associated with cardiovascular disease; however, its underlying mechanisms are not completely understood. Therefore, in the present study, myocardial functions and metabolic changes were investigated using an animal model of CRI in subtotally nephrectomized rats. In addition, some other parameters, considered risk factors of cardiovascular diseases, were determined. Subtotal nephrectomy led to an elevation in blood pressure (144 +/- 2.8 vs 114 +/- 2.5 mm Hg), left ventricular hypertrophy (290 +/- 12 vs 200 +/- 40 mg/100 g b.w.), hypertriglyceridaemia (2.96 +/- 0.31 vs 0.77 +/- 0.07 mmol/l), and impaired glucose tolerance (AUC 836 +/- 12.4 vs 804 +/- 10.4 mmol x l(-1) x 120 min). Isolated perfused hearts of uraemic rats exhibited diminished basal functions (coronary and aortic flow, stroke volume) by 20-30% compared with the controls. Interestingly, the tolerance of isolated heart to global 20-min no-flow ischaemia was improved in uraemic rats. The most marked differences in heart function recovery during reperfusion concerned aortic flow (90 +/- 2.3 vs 66 +/- 10%) and stroke volume (97 +/- 2.7 vs 68 +/- 5.6% of pre-ischaemic values). Pre-ischaemic myocardial glycogen content was distinctly increased (by 50%) in uraemic rats compared with the controls.

Topics: Adenosine Triphosphate; Animals; Female; Glycogen; Heart; Kidney Failure, Chronic; Myocardial Reperfusion Injury; Myocardium; Nephrectomy; Rats; Rats, Wistar

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.

Topics: Adult; Aged; Amino Acids; Energy Metabolism; Female; Glycogen; Glycolysis; Humans; In Vitro Techniques; Kidney Failure, Chronic; Male; Middle Aged; Muscle Fibers, Skeletal; Oxidation-Reduction; Phosphates; Rectus Abdominis

The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of the anterior tibialis muscle was studied in 10 patients with chronic renal failure treated by regular haemodialysis. Repeat muscle biopsies taken when the target haemoglobin concentration of 11 g/dl was achieved showed an increase in median glycogen content from 35 mg/g fat-free dry muscle to 51 mg/g (p < 0.05). The histological appearance showed a marked improvement in muscle fibre diameters, in particular for the type I fibres and a reduction in cytoarchitectural abnormalities. These changes would be expected to produce an increase in both muscle strength and performance and are most probably a consequence of an increase in muscle oxygen delivery.

Topics: Adult; Body Water; Combined Modality Therapy; Erythropoietin; Female; Glycogen; Humans; Kidney Failure, Chronic; Male; Middle Aged; Muscles; Oxygen Consumption; Potassium; Renal Dialysis; Sodium

Persistent symptomatic hypoglycaemia developed in a 26-year-old woman with chronic renal failure. Several factors, including the use of sulfamethoxazole, recent peritoneal dialysis, and poor nutrition may have combined with the defective glycogenolysis and gluconeogenesis present in chronic renal failure to play a role in its aetiology. Increased awareness of this condition is necessary because chronic renal failure is common in the Caribbean.

Topics: Adult; Female; Glycogen; Humans; Hypoglycemia; Kidney Failure, Chronic; Nutrition Disorders

Human polymorphonuclear leukocytes (PMNs) are activated during extracorporeal circulation. An indicator of PMN activation may be the glycogen-degrading enzyme phosphorylase. It is unknown whether dialysis therapy may influence PMN carbohydrate metabolism. Therefore, PMNs were isolated from healthy control subjects, patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and patients undergoing regular hemodialysis therapy (RDT) before, during, and at the end of hemodialysis (HD) treatment using dialyzers made of polysulfone or polymethylmethacrylate (PMMA). Nifedipine (NIF) was continuously infused during HD with PMMA in 5 patients at a dose of 18 micrograms/kg body weight per hour. Glycogen, activity of glycogen synthetase and phosphorylase (active and inactive forms of both enzymes), and glucose uptake with and without stimulation with the chemotactic peptide FMLP were determined in these PMNs. During HD with PMMA, there was a significant increase of PMN phosphorylase "a" activity 15 and 30 minutes after the start of HD. HD with polysulfone did not stimulate the active "a" form of the glycogen-degrading enzyme in PMNs. HD with PMMA significantly inhibited the active I-form of glycogen synthetase, whereas polysulfone activated glycogen synthetase I. NIF inhibited phosphorylase "a" activation during HD with PMMA. PMN glycogen content and glucose uptake were improved during HD with polysulfone, but not with PMMA. PMN glycogen content, activity of glycogen synthetase, and glucose uptake were significantly lower also in CAPD patients compared with healthy controls. These data show that HD with PMMA activates PMN glycogenolysis. This effect can be inhibited by calcium channel blockers. PMN glycogen content of RDT and CAPD patients is significantly lower compared with healthy controls due to inhibition of glycogen synthesis. Elimination of dialyzable factor(s) improves, but does not restore, PMN glycogen synthesis and glucose uptake.

Topics: Adult; Blood Glucose; Glycogen; Glycogen Synthase; Humans; Kidney Failure, Chronic; Membranes, Artificial; Methylmethacrylates; Middle Aged; Neutrophils; Peritoneal Dialysis, Continuous Ambulatory; Phosphorylase a; Renal Dialysis

Topics: Glucose; Glucose Tolerance Test; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Kidney Failure, Chronic; Liver; Receptor, Insulin; Renal Dialysis

Subtotally nephrectomized rabbits were compared with sham-operated controls. The isolated soleus muscle of one leg was exercised using controlled stimulus parameters at 1 Hz until the contraction tension (amplitude) was reduced by one half. The muscle was then quickly frozen in liquid nitrogen and analyzed for lactate, pyruvate, glycogen, alanine, glutamine and alpha-ketoglutarate. The resting leg was used as a control and similarly frozen and analyzed. The difference between resting and exercised muscle lactate and pyruvate concentration was significantly greater in experimental animals while muscle alanine and alpha-ketoglutarate concentrations were lower in the experimental animals. There was no difference in the time required to reach one half of the muscle contraction amplitude between experimental and control animals. Blood lactate levels rose in the experimental animals to a greater degree than in control animals, similar to that seen in human subjects with renal failure.

Topics: Alanine; Animals; Carbohydrate Metabolism; Glutamine; Glycogen; Ketoglutaric Acids; Kidney; Kidney Failure, Chronic; Lactates; Lactic Acid; Muscles; Nephrectomy; Physical Exertion; Pyruvates; Pyruvic Acid; Rabbits

To examine subcellular mechanisms behind the pathogenesis of peripheral insulin resistance in chronic uremic patients, insulin receptor function and glycogen synthase activity were studied in biopsies of skeletal muscle obtained during renal transplant surgery in 9 non-diabetic uremic patients. The results were compared with values obtained in an age- and sex-matched group of subjects with normal renal function, undergoing surgery for urological or gynecological diseases. The recovery of solubilized, wheat germ agglutinin-purified insulin receptors from skeletal muscle was increased among the uremic patients: 49.3 +/- 6.1 vs 31.4 +/- 2.8 fmol/100 mg muscle in healthy controls (p less than 0.03). Basal as well as insulin-stimulated kinase activities of the insulin receptors, expressed as phosphorylation of the synthetic peptide poly(Glu-Tyr(4:1] were similar. In addition, the maximal activity of the glycogen synthase was enhanced in uremic muscle: 26.6 +/- 2.8 vs 19.5 +/- 1.8 nmol.(mg protein)-1.min-1 (p less than 0.05), whereas the half-maximal activation constant for glucose-6-phosphate was identical in the two groups. Likewise, the muscle glycogen concentrations were similar in the uremic patients and the normal controls. In conclusion, our data suggest that neither impaired insulin receptor function nor a reduced maximal glycogen synthase activity of skeletal muscle are involved in the pathogenesis of the insulin resistance of patients with chronic renal failure.

Topics: Adult; Female; Glycogen; Glycogen Synthase; Humans; Insulin Resistance; Kidney Failure, Chronic; Male; Middle Aged; Muscles; Protein-Tyrosine Kinases; Receptor, Insulin

1. Various aspects of carbohydrate metabolism were evaluated in rats exhibiting chronic uremia induced by the surgical removal of 5/6 of the kidneys (NX group). Operated rats developed moderate uremia and maintained a nutritional status similar to that of a sham-operated control group (C rats). 2. After a 12-h fast, the NX group showed a 32% decrease in plasma glucose vs 20% for the C group. 3. After intravenous glucose administration (75 mg/100 mg body weight), plasma glucose and insulin levels were similar in both NX and C rat groups. 4. The decrease in plasma glucose after insulin administration (0.025 U/100 g body weight) was larger in the NX group than in controls. 5. No significant difference was found between the hepatic glycogen levels of NX and C animals although diaphragm muscle glycogen levels in the NX group were nearly twice that of controls. 6. Carcass fatty acid levels in the NX group were 42% lower than in the C group, while total liver lipids were similar for both. 7. These findings suggest that nephrectomized rats exhibit increased sensitivity to exogenous insulin, are not intolerant to intravenous glucose and after a 12-h fast show hypoglycemia that could be related to higher glucose utilization by muscle tissue.

Topics: Animals; Blood Glucose; Fasting; Fatty Acids; Glycogen; Insulin; Kidney Failure, Chronic; Lipid Metabolism; Male; Nephrectomy; Rats; Rats, Inbred Strains; Urea

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: Animals; Blood Urea Nitrogen; Calcium; Creatinine; Cytoplasm; Dogs; Endoplasmic Reticulum; Female; Glycogen; Golgi Apparatus; Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Secondary; Kidney; Kidney Failure, Chronic; Male; Microscopy, Electron; Mitochondria; Nephrectomy; Parathyroid Glands; Phosphates; Phosphorus

Topics: Animals; Chronic Disease; Glycogen; Golgi Apparatus; Kidney Failure, Chronic; Liver; Lysosomes; Mitochondria, Liver; Mitochondrial Swelling; Oxidative Phosphorylation; Rats; Urea; 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: Adult; Aged; Female; Glucose Tolerance Test; Glycogen; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Male; Middle Aged; Pyelonephritis

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