“…Indeed, even plasma insulin levels within the normal range were shown to negatively correlate with the hyperemic response of healthy individuals (1). Although impaired vasodilator function of resistance arteries has been reported in some animal models of insulin resistance (14, 15), the effects of hyperinsulinemia on the matching of O 2 supply with the O 2 need in skeletal muscle have not been determined.Since human red blood cells (RBCs) possess insulin receptors (17,18,49), we hypothesized that insulin itself, via the inhibition of ATP release from RBCs, could contribute directly to vascular dysfunction in prediabetes. Insulin, at levels found in humans with prediabetes (38,40,42,44), has been shown to inhibit ATP release from human RBCs in response to an exposure to reduced PO 2 (27).…”