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.

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