The effects of culture-maintained pancreatic islets on metabolic parameters, renal function, and glomerular lesions in the diabetic rat

Abstract

This study was undertaken for two purposes: to determine whether cultured islets of adult donor rats could be used successfully to reverse the metabolic abnormalities of diabetes of long-term duration and to determine the effect of islet transplantation on renal function and glomerular lesions in diabetic rats. Four groups of rats were studied: (1) five age-matched normal control rats, (2) seven rats with chronic streptozotocin-induced diabetes, (3) six chronically diabetic rats transplant-improved for 3 months, and (4) five acutely diabetic rats transplant-improved for 12 months. Transplanted rats received 1500 culture-maintained adult pancreatic islets injected into the portal vein. Following successful islet transplantation, the metabolic parameters of diabetes, including hyperglycemia, glycosuria, and polyuria, returned to normal. Evaluation of renal function revealed that clearances of isotopic inulin and ϱ-aminohippuric acid were not different among the groups. However, proteinuria was significantly greater in diabetic rats than ir both normal ( p < 0.001) and transplant-improved rats ( p < 0.01). There was striking glomerular immunofluorescence for IgG and C 3 in diabetic rats and none in the other groups. Quantitative morphometric electron microscopy revealed that the glomerular mesangium was significantly greater than normal in diabetic rats and decreased in the transplant-improved rats. The data indicate that culture-maintained islets from adult donors, as previously reported for diabetes of short-term duration, have the capacity to reverse the diabetic process in chronically diabetic rats; and that although rats with chronic diabetes do not exhibit an alteration of glomerular filtration rate, they do develop marked proteinuria, glomerular immunofluorescence, and mesangial thickening, all of which improve following successful islet transplantation.