In previous studies on streptozotocin-diabetic rats, transplantation of 1,000 (but not of 400) pancreatic islets to the renal subcapsular space was followed within 10 days by near-normalization of the impaired insulin secretion and the hyperglycemia. The long-term effects were now studied by measuring insulin and glucagon secretion 3 months after transplantation of 1,000 collagenase-isolated islets in streptozotocin (70 mg/kg) diabetic rats. At this time, diabetic control rats showed marked hyperglycemia and hyperglucagonemia, whereas the basal glucose and glucagon levels had normalized in the transplanted rats. Furthermore, insulin secretion in response to glucose or arginine stimulation and glucagon secretion following arginine stimulation were normal in all transplant rats, but absent in all diabetic controls. Morphologically the transplanted islets in the renal subcapsular space appeared normal on hematoxylin-eosin staining and immunostaining with antisera directed against insulin, glucagon, somatostatin and chromogranin A/B. Thus the islet transplants normalized basal hyperglycemia and hyperglucagonemia and restored insulin and glucagon secretion on a long-term basis.
Animals Arginine