glycogen and Nephrosis

It is known that either arsenic exposure or diabetes can impact renal function. However, it is unclear how these combined factors may influence kidney functions. Therefore, we evaluated morphological, functional, and oxidative parameters in the kidney of diabetic rats exposed to arsenic. Healthy male Wistar rats and streptozotocin-induced diabetic rats were exposed to 0 and 10 mg/L arsenate through drinking water for 40 days. Renal tissue was assessed using morphometry, mitosis and apoptosis markers, mineral proportion, oxidative stress markers, as well as the activity of antioxidant enzymes and membrane-bound adenosine triphosphatases. Arsenate intake altered glucose levels in healthy animals, but it did not reach hyperglycemic conditions. In diabetic animals, arsenate led to a remarkable increase of glycogen nephrosis in distal tubules. In these animals, additionally, the activity of catalase and glutathione S-transferase, besides the proportion of Fe, Cu, and K in renal tissue, was altered. Nevertheless, arsenate did not accumulate in the kidney and did not impact on other parameters previously altered by diabetes, including levels of malondialdehyde, Na, urea, creatinine, and apoptosis and mitosis markers. In conclusion, besides the intensification of glycogen nephrosis, the kidney was able to handle arsenate toxicity at this point, preventing arsenic deposition in the exposed groups and the impairment of renal function.

Topics: Animals; Antioxidants; Apoptosis; Arsenates; Arsenic; Biomarkers; Catalase; Creatinine; Diabetes Mellitus, Experimental; Glycogen; Hazardous Substances; Kidney; Male; Malondialdehyde; Nephrosis; Oxidative Stress; Rats; Rats, Wistar

The important problem of the fate of glycogen-accumulating clear cells in glycogen nephrosis is still unsettled. In this study, we examine whether apoptosis plays a relevant role in the development of diabetic glycogen nephrosis and explore the involvement of the Fas/Fas-L system and the activation of the caspase cascade. Diabetes was induced in rats by streptozotocin injection. Glycogen-accumulating clear cells were identified in renal tissues of hyperglycemic rats. They were found to be concentrated in the thick ascending limbs and distal tubules. Large cellular glycogen accumulations were confirmed by biochemical assays and enzyme-gold cytochemistry. Clear cells displayed apoptotic features such as Annexin V binding, nuclear TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling), and the simultaneous occurrence of Fas, Annexin V, and TUNEL positivity. Western blot analysis demonstrated enhanced expression of Fas receptor/ligand and the activation of the caspase cascade in these cells because cleaved forms of the caspase-3, -8, and -9 were detected. Furthermore, active caspase-3 was located in nuclei by immunoelectron microscopy. Our results indicate that epithelial cells in thick ascending limbs and distal tubules that develop glycogen nephrosis in response to hyperglycemia undergo Fas/Fas-L mediated cell death. Thus, apoptosis could be playing a significant role in renal epithelial cell deletion during diabetes.

Topics: Animals; Annexin A5; Apoptosis; Caspases; Cell Count; Cell Nucleus; Diabetes Mellitus, Experimental; Epithelium; Fas Ligand Protein; fas Receptor; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Immunohistochemistry; Kidney Tubules, Distal; Male; Membrane Glycoproteins; Nephrosis; Rats; Rats, Sprague-Dawley

Glycogen nephrosis, i.e. the Armanni-Ebstein lesion which manifests itself by intracellular accumulation of beta-glycogen has been studied in two groups of streptozotocin diabetic rats and compared to controls. One diabetic group was left untreated and the other diabetic group received pancreatic islet transplantation after 4 weeks duration of diabetes. The kidneys were studied after another 4 week period with normoglycemia. In the non-transplanted diabetic animals glycogen containing tubules comprised 43% of the distal tubule length in the cortex but in the transplanted animals no abnormal, glycogen containing cells could be recovered at the light microscope level. Measurements of the total distal tubule length in the non-transplanted diabetic animals showed that the distal tubules increased in length by 24%. In the transplanted diabetic animals distal tubule length remained the same as in the non-transplanted diabetic animals in spite of normalization of the tubular morphology. This finding could possibly be responsible for the incomplete normalization of kidney weight after treatment.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Female; Glycogen; Islets of Langerhans Transplantation; Kidney; Kidney Tubules; Nephrosis; Organ Size; Rats; Rats, Inbred Lew

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diabetic Nephropathies; Glomerulonephritis; Glycogen; Histocytochemistry; Humans; In Vitro Techniques; Kidney; Kidney Diseases; Microscopy, Electron; Middle Aged; Nephrosis

Topics: Animals; Carbohydrate Metabolism; Diabetes Mellitus, Experimental; Glycogen; Glycogenolysis; Nephrosis; Rabbits

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

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