Effects of Pancreatic Islet Transplantation on the Increased Urinary Albumin Excretion Rates in Intact and Uninephrectomized Rats with Diabetes Mellitus

Abstract

The effects of reduced renal mass and of islet transplantation on urinary albumin excretion (UAE) rates in diabetic rats were examined. Increased UAE rates were noted two months after the induction of streptozotocin diabetes in 100-gm. inbred Lewis rats. Over the subsequent seven months, UAE rates remained constant in controls but were increasing in diabetic rats at the end of this time. Uninephrectomized nondiabetic rats had increasing UAE with time as compared with intact controls. Uninephrectomized diabetic rats had greater UAE than their respective controls, and the magnitude of this difference increased over the nine-month period of these studies. Uninephrectomized and intact rats, diabetic for seven months, were cured of the diabetic state by neonatal pancreatic tissue administered via the portal vein. Within one month of transplantation, UAE values decreased in these animals as compared with their pretransplant values and, within two months, were no longer different from values in their respective nondiabetic controls. In contrast, untreated uninephrectomized and intact diabetic rats increased their UAE over these same two months. At two months posttransplant, glomerular mesangial thickening was decreased in transplanted uninephrectomized and intact diabetic rats when compared with their respective untreated diabetic littermates.Thus, the albuminuria of diabetes in rats is reversed by pancreatic islet transplantation. It is unclear whether this reversal is primarily due to improvement in functional or structural abnormalities in glomeruli of diabetic rats. DIABETES 27:959-64, September, 1978.The pathogenesis of increased urinary albumin excretion in experimental and human diabetes mellitus is unclear. The clinical course of juvenile-onset diabetic patients dying of diabetic nephropathy has been characterized by the development of persistent albuminuria (more than 20 mg./lOO ml. in random urine specimens) after a mean duration of diabetes of 17.3 years. 1 This was followed, on the average, by early renal failure within two years and by death from renal failure within four years. 1 In another study, 2 although the duration of proteinuria before the onset of early renal failure was variable, the frequency of azotemia approached 50 per cent within five years of the onset of proteinuria; of 25 patients developing From the

The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus

“…These include increased glomerular filtration rate (GFR) [1-13], increased urinary albumin excretion (UAE) [13][14][15][16][17], increased production of vasoactive prostaglandins (PGs) by renal glomeruli [10,[18][19][20], and increased glomerular sorbitol accumulation [21]. Although there are several plausible ways in which these changes could be related, the data linking these phenomena have been conflicting and confusing.…”

Pancreas and islet transplantation

“…The influence of islet transplantation on established renal glomerular lesions has been shown in a series of experiments in diabetic rats by Mauer et al [167,281,289] and Steffes et at. [282,290].…”

“…The latent period between transplantation and reversal of diabetes also depends upon the quantity of tissue transplanted, the site of transplantation, and the severity of diabetes [113,123,166]. The period can range from a few days to weeks, but if a sufficient quantity of dispersed neonatal pancreas is transplanted, permanent normoglycaemia occurs [110-117, 142, 166-168], glycosuria is abolished [110,116,123,168], weight gain is restored [110,113,116,166], and other metabolic abnormalities disappear [142,167,168].…”

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“…During the period of study for 5 weeks normal animals showed a rise in Urinary albumin levels. This indicates progressive nephropathy 18,19 . The treatment with MESA has shown the protective effect on the elevated Urinary albumin level.…”