α-Adrenergic Blockade Improves Glucose-Potentiated Insulin Secretion in Non-Insulin-Dependent Diabetes Mellitus

Abstract

The impairment of glucose-potentiated insulin secretion present in non-insulin-dependent diabetes mel I it us (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L-arginine. Glucose-potentiated insulin secretion was determined on separate days during α-, β-, and combined α- plus β-adrenergic blockade and compared with a saline control. In. normal subjects, there was no effect of α-, β-, or α- plus β-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 ± 0.06 μU · ml−1 · mg−1 · dl, mean ± SE; P < .01) was not affected by β-blockade but increased during α-blockade (0.91 ± 0.22 μU · ml−1 · mg−1 · dl; P < .05). However, this improvement was abolished by combined α- plus β-blockade (0.32 ± 0.07 μU · ml−1 · mg−1 dl). Plasma norepinephrine was increased above basal levels in both normal (+ 260 ± 89 pg/ml) and NIDDM (+ 438 ± 162 pg/ml) subjects during α-blockade (P < .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration. These results suggest that the increase in glucose-potentiated insulin secretion during α-adrenergic blockade was a result of both a decrease in an endogenous overactive α-adrenergic stimulation and an increase in synaptic cleft norepinephrine levels, which resulted in an increase in islet β-adrenergic stimulation. We suggest that a chronic decrease in islet α-adrenergic stimulation may prove to be a useful adjunct to NIDDM management.