Prevention of hyperglycemia improves the long-term result of islet transplantation in streptozotocin-diabetic rats.

We examined the hypothesis that prevention of hyperglycemia during the critical period immediately following islet transplantation will improve the outcome of the transplantation in streptozotocin-diabetic rats. Two days after intravenous injection of streptozotocin (70 mg/kg), 400 or 1,000 islets were transplanted into the left kidney subcapsular space. A group of rats transplanted with 400 islets was treated with insulin from 1 day before transplantation and for 7 days. Intravenous glucose infusion was performed at 10 days and 3 months after transplantation. In addition, at 3 months, the grafts were examined by light and electron microscopy. We found that rats transplanted with 400 islets without any concomitant insulin administration remained diabetic throughout the 3-month period and no plasma insulin response was induced by glucose infusion in these rats. In contrast, diabetic rats transplanted with 400 islets and treated with insulin for 7 days remained normoglycemic throughout the 3-month period, as did rats transplanted with 1,000 islets. Furthermore, these rats had normal glucose-stimulated insulin secretion both at 10 days and at 3 months after transplantation. Moreover, islet grafts from rats transplanted with 400 islets and administered insulin as well as from rats transplanted with 1,000 islets were morphologically normal, and following removal of the graft, hyperglycemia developed rapidly. In contrast, the islet grafts from rats transplanted with 400 islets without concomitant insulin administration had only few insulin cells. Thus, by preventing hyperglycemia at the time of islet transplantation, the long-term result of islet transplantation was improved. Therefore, the ambient glucose level initially following islet transplantation is critical for the long-term result.