Abstract P1122: Sympathetic Vasodilation Improves Insulin-Mediated Microvascular Recruitment in the Forearm of Obese Subjects

Abstract

Background: Obesity is associated with sympathetic activation which results in insulin resistance and a blunted insulin-mediated microvascular recruitment. We propose that removal of sympathetic vasoconstriction can result in improvement of insulin-mediated vasodilation and subsequently in sensitivity to insulin-mediated glucose uptake. Methods: We blocked sympathetic vasoconstriction in an isolated forearm model during a hyperinsulinemic euglycemic clamp to determine the effect of insulin recruitment on microvascular circulation using contrast-enhanced ultrasonography (CEU). We studied 9 obese human subjects (age 41±6 years, BMI 37±3 kg*m -2 , SBP 125±6 mm Hg). We assessed the effects of insulin on microvascular recruitment and glucose uptake on two separate occasions, randomly assigned and at least one month apart, during an intrabrachial infusion of the alpha-adrenergic blocker phentolamine (PHE, 25 micrograms/min, blocked day) or saline (SAL, Control day). Subjects were studied at baseline (BSL) and at the end of the clamp (CLAMP). Results: As expected forearm blood flow increased after insulin alone (67±27%, p=0.016) and with alpha blockade and insulin (140± 22%, p=0.0011). Microvascular blood volume (MBV, index of microvascular recruitment), showed a significant increased during PHE compared to SAL (figure). Muscle glucose uptake trended towards increase with PHE but did not reach statistical significance (p=0.0558). There were no systemic effects due to sympathetic blockade. Conclusions: This data shows that sympathetic vasoconstriction contributes to the blunted insulin-mediated microvascular recruitment seen in obesity.