Interaction of Glucose and Epinephrine in the Regulation of Insulin Secretion

Abstract

To determine whether the elevated plasma glucose levels produced by epinephrine (EPI) in vivo offset important islet effects of EPI in man, the acute insulin responses (AIR: IRI Δ 2–5 min) to 5 g i.v. arginine were measured at varying EPI and glucose levels. After infusion of EPI at 80 ng/kg/min for 45 min, achieving venous plasma EPI levels of 1140 ± 121 pg/ml, the AIR was indistinguishable from that seen in 10 untreated subjects (EPI versus untreated: 59 ± 11 versus 41 ± 5 μU/ml, ± SEM, P = NS), but plasma glucose had risen to 165 ± 8 mg/dl. When this glucose rise was matched in each subject by a glucose clamp infusion (GLU) with no EPI infusion, AIR increased to 467 ± 82% of that during EPI (N = 8, P < 0.001). With glucose subsequently clamped at a higher level, 256 ± 5 mg/dl, the AIR to arginine during GLU alone was 220 ± 17% of that during EPI + GLU (N = 7, P < 0.001). A qualitatively similar inhibitory effect on AIR to arginine was also observed using a lower dose of EPI (15 ng/kg/min, giving a venous plasma EPI level of 192 ± 19 pg/ml). To quantitate the opposing effects of plasma glucose and EPI on the AIR to arginine, a multiple linear regression analysis using glucose and EPI levels was performed. This analysis showed that AIR is positively correlated with plasma glucose (P < 0.001), negatively correlated with log [EPI] (P < 0.001), and negatively correlated with their product, glucose × log [EPI] (P < 0.01). The changes in glucose and EPI explained 90% of the variation in AIR observed within each subject (R2 = 0.896). These studies demonstrate that EPI inhibits AIR to arginine over a wide range of glucose levels, but that the B-cell-stimulating effect of hyperglycemia can obscure this inhibition. The data suggest that the development of hyperglycemia during stress states may compensate for the inhibitory effect of EPI on B-cell function, thereby maintaining normal basal and stimulated insulin levels.