Alterations in carbohydrate metabolism and insulin resistance are major features of the metabolic response to injury. The mediators of these changes are not defined. In this study we investigated the influence of epinephrine on insulin-mediated glucose uptake by peripheral tissue. Forearm blood flow and substrate exchange were determined during insulin clamp studies with and without epinephrine infusion in normal persons. During control studies insulin concentration was raised to 103 +/- 5 microU/ml. Whole body glucose disposal was 9.23 +/- 1.01 mg/kg . min. At a comparable level of hyperinsulinemia (93 +/- 4 microU/ml), epinephrine reduced glucose disposal to 4.54 +/- 0.39 mg/kg . min (P less than 0.01). Forearm glucose uptake was reduced from 0.66 +/- 0.08 to 0.18 +/- 0.13 mg/100 ml . min (P less than 0.05) despite a doubling of forearm blood flow. Epinephrine reduces whole body glucose disposal in part by reducing glucose uptake in peripheral tissue, primarily muscle. Epinephrine-induced skeletal muscle insulin resistance may play a major role in insulin-resistant states and may contribute to accelerated protein catabolism seen following injury.
