Functional insulin receptors are known to occur in pancreatic beta cells; h
owever, except for a positive feedback on insulin synthesis, their physiolo
gical effects are unknown. Amperometric measurements at single, primary pan
creatic beta cells reveal that application of exogenous insulin in the pres
ence or absence of nonstimulatory concentrations of glucose evokes exocytos
is mediated by the beta cell insulin receptor. Insulin also elicits increas
es in intracellular Ca2+ concentration in beta cells but has minimal effect
s on membrane potential. Conditions where the insulin receptor is blocked o
r cell surface concentration of free insulin is reduced during exocytosis d
iminishes secretion induced by other secretagogues, providing evidence for
direct autocrine action of insulin upon secretion from the same cell. These
results indicate that the beta cell insulin receptor can mediate positive
feedback for insulin secretion. The presence of a positive feedback mechani
sm for insulin secretion mediated by the insulin receptor provides a potent
ial Link between impaired insulin secretion and insulin resistance.