VASOCONSTRICTION WITH NOREPINEPHRINE CAUSES LESS FOREARM INSULIN-RESISTANCE THAN A REFLEX SYMPATHETIC VASOCONSTRICTION

We used the insulin-perfused human forearm model to assess the effects of vasoconstriction induced with norepinephrine on the extraction of glucose in the forearm in two groups of healthy young volunteers. The norepinephrine findings were compared with a previously studied group in which vasoconstriction had been caused by reflex activation of the sympathetic nervous system. The aim of the study was to determine the relative importance of hemodynamic and receptor-mediated mechanisms of insulin resistance. Plasma insulin, arterial and venous glucose sampl es, and forearm blood flow were measured at 10-minute intervals during a 30-minute baseline, a 60-minute intra-arterial insulin infusion, an d during 30 minutes of insulin infusion plus vasoconstriction. Group 1 (n=14) had physiological vasoconstriction induced by inflation of bil ateral thigh cuffs to 40 mm Hg to cause pooling of blood in the lower extremities and reflex vasoconstriction in the forearm; group 2 (n=8) had intra-arterial infusion of norepinephrine to achieve the same degr ee of vasoconstriction as seen with inflation of thigh cuffs in group 1. Subjects in group 3 (n=7) had infusion of intra-arterial norepineph rine to achieve a twofold increase in physiological vasoconstriction. With a physiological decrease in forearm blood flow (group 1), there w as a 19% decrease in forearm blood flow resulting in a 23% reduction i n glucose uptake in the forearm (P<.03). The same degree of reduction in forearm blood flow with a predominantly alpha-adrenergic agonist, n orepinephrine (group 2), causes much less insulin resistance (a decrea se in utilization of 13%) (P<.04). When forearm blood flow is decrease d twofold over the physiological vasoconstriction (group 3), there is a 42% reduction in glucose uptake (P<.005). The larger degree of insul in resistance with mild (25%) reflex vasoconstriction when compared wi th an equal degree of vasoconstriction induced by norepinephrine may b e due to activation of beta-receptors during the reflex or to differen ces in the microcirculatory patterns with different modalities of vaso constriction.