The purposes of this study were to determine whether patients with non-insulin-dependent diabetes mellitus (NIDDM) have an enhanced glycemic response to epinephrine (EPI) and to quantitate the effect of physiological elevations of EPI on pancreatic islet function in these patients. The increment of plasma glucose (PG) in response to 45 min of EPI infusion (mean plasma EPI 2490 pM) was more than twofold greater in nine NIDDM patients than in 20 nondiabetic control subjects (mean ± SE ΔPG 3.9 ± 0.3 vs. 1.7 ± 0.1 mM, P < 0.0001). The effects of EPI on β-cell and α-cell function were compared in nine NIDDM patients and 9 age- and weight-matched control subjects during infusions of saline or two doses of EPI on separate days (mean plasma EPI 270, 1120, and 2490 pM). On each day, the acute insulin response (AIR) and acute glucagon response (AGR) to 5 g i.v. arginine were measured at three matched steady-state PG levels (means of 9, 14, and 29 mM). β-cell sensitivity to glucose (slope of glucose potentiation) and β-cell secretory capacity, or AIRmax (AIR at the highest clamped PG level), were calculated. In control subjects, EPI inhibited the AIR at PG concentrations of 9 and 14 mM (both P < 0.05) but had no effect on the AIRmax, resulting in a rightward shift of the curve relating the AIR and PG and a decrease in the slope of glucose potentiation (P < 0.01). In contrast in NIDDM patients, EPI inhibited the AIR at all PG levels, including the AIRmax (all P < 0.05). EPI enhanced the AGR at all PG levels in control subjects but had no consistent effect on the AGR in patients with NIDDM. Multiple linear regression analysis demonstrated that, in both groupos, the AIR was significantly influenced by varying PG and EPI levels, together explaining >50% of the variation of AIR. These studies indicate that 1) the hyperglycemic effect of EPI is increased in patients with NIDDM, 2) EPI decreases β-cell sensitivity to glucose in control subjects and may also decrease maximal β-cell secretory capacity in NIDDM, and 3) EPI has no consistent effect on α-cell function in NIDDM. These findings suggest that the stress of intercurrent illness may induce a greater derangement of glycemic control in NIDDM patients than in nondiabetic humans, due in part to the failure of hyperglycemia to adequately compensate for the inhibitory effect of EPI on β-cell function.

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