REFLEX SYMPATHETIC ACTIVATION INDUCES ACUTE INSULIN RESISTANCE IN THEHUMAN FOREARM

Inferences about the association between sympathetic overactivity and insulin resistance, have been drawn from the infusion of sympathomimet ic amines in supraphysiological doses. We used the isolated perfused h uman forearm to investigate the effect of reflex-induced sympathetic n ervous system activation on the peripheral utilization of glucose in t he skeletal muscles of 14 healthy men. Local hyperinsulinemia in the f orearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg . dL-1 . min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg . dL-1 . min-1 per 100 mL forearm volume) between 40 and 60 minute s of insulin infusion but did not alter the utilization of oxygen. Ref lex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 m m Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (ave rage decrease of 19%, p<0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23% , p<0.02), whereas oxygen utilization was unchanged. We find that an i ncrease in sympathetic nervous system activation (within the normal ra nge of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxyg en utilization, but the same stimulus elicited a decrease in the utili zation of glucose. The decrease in utilization of glucose in skeletal muscle may be caused by both the decrease in blood flow and by an adre nergic receptor-mediated resistance. The relative contributions of eac h of these mechanisms to insulin resistance deserves further investiga tion.