Influence of long-term diabetes on renal glycogen metabolism in the rat.
OBJECTIVE
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 of 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 levels, low insulin but normal glucagon concentrations in portal blood. In the fasting state, kidney glycogen content was very low in both young control and young diabetic rats (54 +/- 15 and 189 +/- 26 microg/g, respectively, mean +/- 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 microg/g of diabetic rat, fasting and fed, respectively, p < 0.001 vs. 0 +/- 0 and 4 +/- 6 microg/g of control rats). On electron microscopy, large glycogen clusters were localized to the renal tubules. Kidney phosphorylase activity was higher, and synthase activity lower in diabetic than control rats (p < 0.05 for both), whereas kidney glycogen was strongly related to plasma glucose levels, suggesting that the enzyme changes were secondary to glycogen accumulation itself. Renal hexosephosphates and fructose-2,6-bisphosphate contents were both increased in long-term diabetic rats (p < 0.05), implying enhanced fluxes through both glycolysis and gluconeogenesis.


CONCLUSIONS
In chronic, untreated diabetes glycogen accumulates in the renal tubules; prolonged hyperglycemia is the sole driving force for this phenomenon.
Nannipieri
M
M
Department of Internal Medicine, University of Pisa School of Medicine, Via Savi 8, I-56100 Pisa, Italy.
Lanfranchi
A
A
Santerini
D
D
Catalano
C
C
Van de Werve
G
G
Ferrannini
E
E
D000375:Aging / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D006003:Glycogen / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D007686:Kidney Tubules, Distal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006003:Glycogen