Effects of yohimbine and nicotinic acid on insulin secretion in islet transplanted streptozotocin-diabetic rats

Abstract

Whether insulin secretion from transplanted islets is normally regulated has not been established. We have studied the effects of either alpha-adrenoceptor antagonism or induction of insulin resistance on glucose-stimulated insulin secretion in streptozotocin (70 mg/kg)-diabetic rats transplanted with 1000 freshly isolated islets to the left kidney subcapsular space. The alpha 2-adrenoceptor antagonist yohimbine (15 micrograms/min) increased basal and potentiated glucose-stimulated insulin secretion in control rats. In contrast, yohimbine did not affect basal or glucose-stimulated insulin secretion in transplanted rats. This suggests that the alpha-adrenoceptor islet tonus is lost following islet transplantation. Induction of insulin resistance by nicotinic acid (6 mg orally twice daily for 10 days) was followed by increased basal insulin levels without any effect on basal plasma glucose levels, both in control and islet transplanted rats, as an adaptation to insulin resistance. Furthermore, after nicotinic acid, the plasma insulin response during glucose infusion was adequate to maintain the normal hyperglycemic response, both in controls and in islet transplanted rats. This suggests that transplanted islets retain the capability to adapt to insulin resistance.