EFFECTS OF EPINEPHRINE ON INSULIN-MEDIATED GLUCOSE-UPTAKE IN WHOLE-BODY AND LEG MUSCLE IN HUMANS - ROLE OF BLOOD-FLOW

In vivo insulin-mediated glucose uptake (IMGU) occurs chiefly in skeletal muscle, where it is determined by the product of arteriovenous glucose difference (DELTA-AVG) and blood flow (BF) rate into muscle. Epinephrine (Epi) reduces the rate of IMGU in whole body. To examine whether this is due to a reduction in DELTA-AVG across or BF into skeletal muscle we constructed insulin dose-response curves for whole body IMGU and leg muscle IMGU using euglycemic clamp (+[3-H-3]glucose infusion) and leg balance techniques during insulin infusions ranging from 10 to 1,200 mU.m-2.min-1. We studied six subjects [wt 70 +/- 2 (SE) kg] during an Epi infusion at a single rate of 0.002 mg.kg-1.min-1 and six subjects (70 +/- 3 kg) during a saline infusion alone. Maximum whole body glucose uptake (WBGU) was similar during Epi and saline infusions [71.4 vs. 73.6 mmol.kg-1.min-1, P = not significant (NS)]. Compared with saline, maximum DELTA-AVG was decreased during Epi infusion (1.04 vs. 1.31 mM, P < 0.01). Compared with saline alone maximum leg BF was increased (5.3 vs. 4.3 dl/min, P < 0.01) during Epi infusion. Thus maximum leg glucose uptake (LGU) was similar (696 vs. 821 pmol.leg-1.min-1, P = NS) during infusion of Epi and saline, respectively. Half-maximal effective dose for insulin's effect to stimulate WBGU, DELTA-AVG, BF, and LGU was increased two- to threefold during Epi vs. saline infusions (P < 0.01 for all values). Thus 1) Epi decreases insulin's effect to increase skeletal muscle glucose extraction (DELTA-AVG) at all insulin concentrations; 2) Epi causes a shift to the right of insulin dose-response curves for WBGU, DELTA-AVG, BF, and LGU; and 3) at high insulin concentrations Epi-induced increments in BF compensate for decreases in DELTA-AVG to normalize maximal rates of glucose uptake. In conclusion, effects of Epi on insulin action are complex and depend on proportional decreases in muscle glucose extraction and increases in muscle BF at each insulin concentration.