LONG-TERM ISOGRAFTS OF CULTURED FETAL MOUSE PANCREATIC-ISLETS - THE ONCOGENIC EFFECTS OF STREPTOZOTOCIN AND THE PREVENTION OF DIABETIC RENAL COMPLICATIONS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 104  (3) , 227-236
Abstract
Female CBA mice made diabetic with a single i.v. dose of streptozotocin (STZ) were either grafted with cultured fetal mouse pancreatic islets onto the splenic capsule, treated with insulin, or left untreated. An age- and sex-matched group of nondiabetic mice served as normal controls. All islet-grafted and most insulin-treated mice survived and had normal fasting blood glucose levels. Of the untreated diabetic mice, 1 died and the survivors showed poor weight gain. Light-microscopic examination of the islet isografts showed a progressive increase in graft size and .beta.-cell granulation over the 9-mo. study period. Quantitative EM examination of the kidney showed that, whereas the islet-grafted and nondiabetic control mice had similar glomerular capillary basement membrane (GCBM) thickness, the untreated diabetic and insulin-treated mice had markedly thickened GCBM. All STZ-treated mice developed diffuse hepatic dysplasia and, at later time points, some showed biliary hyperplasia, intrahepatic cysts and occasionally nodular dysplasia. With increasing time after STZ, most mice developed renal adenomas. One untreated diabetic mouse also developed a solitary functional pancreatic .beta.-cell adenoma. STZ effects were not affected by treatment of diabetes.