Abnormal Glucose Regulation of Insulin Secretion in Models of Reduced B-Cell Mass

The influence of glucose on nonglucose-stimulated in sulin secretion was examined in two animal models with reduced B-cell mass: rats treated with streptozotocin as neonates (SZ) and rats with a partial pancreatectomy (Px). The effects of arginine and IBMX upon insulin secretion were studied at varying glucose con centrations using the in vitro, isolated, perfused pan creas. In normal rats, as expected, 16.7 mM glucose caused a biphasic insulin release and arginine-stimulated in sulin secretion was markedly potentiated by an in crease in background glucose concentration. In the SZ model, 16.7 mM glucose caused a minimal insulin re sponse. However, arginine stimulated insulin release at 2.8 mM glucose as well as at higher glucose concen trations. A similar alteration in the glucose regulation of insulin secretion was shown with another secret agogue, IBMX, even though responses to this agent in the SZ rats exceeded those of the controls at both high- and low-background glucose concentrations. The less diabetic, Px model showed partial preservation of the glucose regulation of the B-cell response to arginine. Thus, a reduction in B-cell mass leads not only to a toss of glucose-stimulated insulin secretion but also to impaired glucose regulation of nonglucose-stimulated insulin secretion.