Insulin Sensitivity of Muscle Capillary Recruitment In Vivo

Insulin Sensitivity of Muscle Capillary Recruitment In Vivo Lei Zhang 1 , Michelle A. Vincent 2 , Stephen M. Richards 1 , Lucy H. Clerk 2 , Stephen Rattigan 1 , Michael G. Clark 1 and Eugene J. Barrett 2 1 Department of Biochemistry, University of Tasmania, Hobart, Tasmania, Australia 2 Department of Internal Medicine, University of Virginia, Charlottesville, Virginia Address correspondence and reprint requests to Eugene J. Barrett MD, PhD, Box 801410, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail: ejb8x{at}virginia.edu Abstract We have reported that insulin exerts two vascular actions in muscle; it both increases blood flow and recruits capillaries. In parallel hyperinsulinemic-euglycemic clamp studies, we compared the insulin dose response of muscle microvascular recruitment and femoral blood flow as well as hindleg glucose uptake in fed, hooded Wistar and fasted Sprague-Dawley rats. Using insulin doses between 0 and 30 mU −1 · min −1 · kg −1 , we measured microvascular recruitment at 2 h by 1-methylxanthine (1-MX) metabolism or contrast-enhanced ultrasound (CEU), and muscle glucose uptake was measured by either arteriovenous differences or using 2-deoxyglucose. We also examined the time course for reversal of microvascular recruitment following cessation of a 3 mU · min −1 · kg −1 insulin infusion. In both groups, whether measured by 1-MX metabolism or CEU, microvascular recruitment was fully activated by physiologic hyperinsulinemia and occurred at lower insulin concentrations than those that stimulated glucose uptake or hindleg total blood flow. The latter processes were insulin dose dependent throughout the entire dose range studied. Upon stopping the insulin infusion, increases in microvascular volume persisted for 15–30 min after insulin concentrations returned to basal levels. We conclude that the precapillary arterioles that regulate microvascular recruitment are more insulin sensitive than resistance arterioles that regulate total flow. 1-MX, 1-methylanthine 2DG, 2-deoxy-d-[2,6-3H]glucose CEU, contrast-enhanced ultrasound Footnotes Accepted November 6, 2003. Received July 29, 2003. DIABETES