Influence of Long-Term Diabetes on Renal Glycogen Metabolism in the Rat

Abstract

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 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 µg/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 µg/g of diabetic rat, fasting and fed, respectively, p < 0.001 vs. 0 ± 0 and 4 ± 6 µg/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. Conclusion: In chronic, untreated diabetes glycogen accumulates in the renal tubules; prolonged hyperglycemia is the sole driving force for this phenomenon.

Apoptosis of Tubular Epithelial Cells in Glycogen Nephrosis During Diabetes

“…The glycogen nephrosis, characteristic of diabetic nephropathy, has been extensively investigated (Holck and Rasch, 1993;Meyer et al, 1998;Nannipieri et al, 2001;Rasch, 1984Rasch, , 1991. Rasch and Holck (Holck and Rasch, 1993;Rasch, 1984Rasch, , 1991 reported that the lesion is confined to the distal tubules, including the thick ascending limbs (TALs) in the cortex and the outer stripe of the outer medulla (OSOM).…”

Attenuation of Armanni–Ebstein lesions in a rat model of diabetes by a new anti-fibrotic, anti-inflammatory agent, FT011

“…A key morphological change associated with sustained hyperglycaemia in the diabetic kidney is the accumulation of glycogen [1], known as Armanni-Ebstein lesions [2]. Glycogen accumulation predominantly occurs in the cortical and outer medullary region of the diabetic kidney, primarily localised in the thick ascending limb of the loop of Henle and distal tubules [1].…”

“…Glycogen accumulation predominantly occurs in the cortical and outer medullary region of the diabetic kidney, primarily localised in the thick ascending limb of the loop of Henle and distal tubules [1]. The accumulation of glycogen in these cells has been suggested by several studies to compromise their viability and thus contribute to renal impairment in diabetic individuals [2].…”

“…The accumulation of glycogen in these cells has been suggested by several studies to compromise their viability and thus contribute to renal impairment in diabetic individuals [2]. Furthermore, a growing body of evidence suggests that glycogen nephrosis may be associated with the progression of diabetic nephropathy [1,3].…”

Redistribution of Integrins in Tubular Epithelial Cells during Diabetic Glycogen Nephrosis

“…Numerous studies have described the characteristics of glycogen nephrosis [4, 5, 7, 23, 24]. However, none has addressed the possible alterations in cell-to-matrix interactions for these glycogen-accumulating clear cells.…”