POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

Abstract

ABSTRACT Glucose-induced potentiation of glucose-induced insulin release was quantitatively evaluated in 14 non-obese subjects with normal glucose tolerance but decreased insulin response, and in six non-obese patients with mild, adult-onset diabetes, by measuring the insulin responses to two consecutive glucose infusion tests, administered with 40 or 70 min interval. Enhancement of the second insulin response occurred in both groups. In low insulin responders, the dose-response relationship between blood glucose and plasma insulin was flatter and shifted to the right when compared to the control. Pretreatment with glucose increased strikingly the slope of this relationship, the responses now being within the normal range. The enhancement induced by glucose seems to be of multiplicative type. In mildly diabetic subjects, insulin response to glucose infusion was low and sluggish, only a minor initial response being observed. Pretreatment with glucose modified the profile of the insulin response, a clear-cut initial response of greater magnitude being obtained at least in some of the patients. The sensitivity of the islet to the potentiating action of glucose was higher in low insulin responders than in controls, the minimal glucose concentration needed to induce potentiation of the forthcoming response being much lower. The dose-response curve for the relationship between the blood glucose level of the preinfusion period and the percentual enhancement of the insulin response obtained at the second stimulation was, in low insulin responders, higher than and shifted to the left of the curve of the control subjects. In the group of diabetics, sensitivity for potentiation by glucose seemed not different from the controls. These studies indicate that the ability of glucose to initiate insulin release and its ability to generate time-bound potentiation in the islet correspond to two distinct functions. In the early stages of the diabetic syndrome, only the recognition of glucose as the initiator of an insulinogenic signal is impaired. The pancreatic beta-cell in these subjects seems to recognize normally glucose as the promotor of the potentiation.