The effect of epinephrine on glucose-mediated and insulin-mediated glucose disposal in insulin-dependent diabetes

Abstract

The aim of this study was to determine the relative roles of changes in glucose-mediated glucose disposal (SG) and insulin sensitivity (SI) on the impairment of glucose disposal caused by epinephrine (EPI) infusion in type I (insulin-dependent) diabetes mellitus (IDDM). Seven non-obese young adult diabetics with minimal endogenous insulin secretion had EPI infusions at 25 ng/kg/min for 5.5 hours, after a basal overnight insulin infusion (12 mU/kg/h), and glucose infusion as required to maintain euglycemia. The EPI infusion produced approximately an eightfold increase in plasma EPI. At 2.5 hours, an intravenous glucose tolerance test (IVGTT) was performed with supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. In random order, each subject also had a control (CTR) infusion of basal insulin before the IVGTT. The results were analyzed according to a modification of the minimal model of Bergman et al. EPI infusion was associated with (1) elevated basal plasma glucose (EPI v CTR, 9.8 ± 0.3 SE v 7.7 ± 0.7 mmol/L, P < .05); (2) elevated plasma nonesterified fatty acids (NEFA, 0.9 ± 0.1 v 0.3 ± 0.1 mmol/L, P < .05); and (3) profoundly reduced glucose disposal (K G 0.59 ± 0.1 v 1.91 ± 0.33 min −1 × 10 2, P < .02). Further analysis showed that the reduced glucose disposal was attributable to a marked decrease in SI (EPI 0.9 ± 0.5 v CTR 7.03 ± 3.2 min −1 · mU −1 · L × 10 4, P < .05) with no significant change in SG (EPI 2.5 ± 0.2 v CTR 3.1 ± 0.5 min −1 × 10 2, NS). These results show that physiological EPI elevation in IDDM impairs insulin-mediated, but not glucose-mediated, glucose disposal.