Influence of long-term diabetes on renal glycogen metabolism in the rat

Background/Aims: The effects of acute insulin deficiency on the kidney have been investigated in animal models of experimental diabetes; however, the impact of long-term diabetes has not been determined. Methods: We measured renal glycogen contents in streptozotocin (STZ)-diabetic rats 3 weeks (n = 12) or 9 months (n = 12) after the induction of diabetes, and in 2 groups o f control rats of similar age (n = 16 and n = 12, respectively), in the fed state and after a 24-hour fast. Results: Diabetic rats had high glucose le vels, low insulin but normal glucagon concentrations in portal blood. In th e fasting state, kidney glycogen content was very low in both young control and young diabetic rats (54 +/- 15 and 189 +/- 26 mug/g, respectively, mea n +/- SD); in contrast, glycogen levels were markedly elevated in rats with long-standing diabetes as compared to old nondiabetic animals (2,628 +/- 1 ,023 +/- and 1,968 +/- 989 mug/g of diabetic rat, fasting and fed, respecti vely, p < 0.001 vs. 0 +/- 0 and 4 +/- 6 <mu>g/g of control rats). On electr on microscopy, large glycogen clusters were localized to the renal tubules. Kidney phosphorylase activity was higher, and synthase activity lower in d iabetic than control rats (p ( 0.05 for both), whereas kidney glycogen was strongly related to plasma glucose levels, suggesting that the enzyme chang es were secondary to glycogen accumulation itself. Renal hexosephosphates a nd fructose-2,6-bisphosphate contents were both increased in long-term diab etic rats (p < 0.05), implying enhanced fluxes through both glycolysis and gluconeogenesis. Conclusion: In chronic, untreated diabetes glycogen accumu lates in the renal tubules; prolonged hyperglycemia is the sole driving for ce for this phenomenon. Copyright (C) 2001 S. Karger AG, Basel.