Differential Vasomotor Effects of Insulin in the Peripheral and Cerebrovascular Circulations of Healthy Young Adults

Abstract

Background Insulin-stimulated peripheral and cerebrovascular vasodilation are consistently observed in preclinical animal models. Hyperinsulinemia also has profound vasodilatory effects within the skeletal muscle vasculature in healthy young adults; however, the magnitude of insulin-stimulated cerebrovascular vasodilation in humans remains unclear. We hypothesized insulin-stimulated vasodilation would be observed in both the peripheral and cerebral circulations in healthy young adults. Methods Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in 9 healthy young adults (4M/5F, 28±2 yrs, 24±1 kg/m2) at baseline and following a 60-min hyperinsulinemic (40 mU/m2 body surface area/min), euglycemic infusion. Femoral artery diameter and mean blood velocity were measured by Doppler ultrasound to determine femoral artery blood flow (FBF). Mean arterial blood pressure (MABP) was measured continuously by finger photoplethysmography. Cerebrovascular conductance index (CVCi = MCAv/MABP x 100) and femoral vascular conductance (FVC = FBF/MABP x 100) were calculated. Results Intravenous insulin infusion resulted in an increase in plasma insulin (5±1 to 41±2 µIU/mL, p<0.01) with blood glucose maintained at baseline levels (75±2 to 72±4 mg/dL, p=0.48). MABP was maintained throughout the infusion protocol (85±3 to 88±3 mmHg, p=0.21). There was a significant increase in FBF (134±24 to 184±30 mL/min, p=0.05) and FVC (153±22 to 211±31 mL/min/100 mmHg, p=0.04) during hyperinsulinemia. In contrast, there was no effect of hyperinsulinemia on MCAv (54±3 to 51±3 cm/s, p=0.28) or CVCi (65±5 to 58±3 AU, p=0.14). There was no association between insulin-stimulated peripheral and cerebrovascular vasodilation (R=-0.421, p=0.26). Conclusions Hyperinsulinemia in healthy young adults elicits peripheral vasodilation. Contrary to our hypothesis, following a 60-minute systemic intravenous insulin infusion there is no change in MCAv or CVCi in healthy young adults. These data indicate the cerebral and peripheral vasculature are differentially regulated during hyperinsulinemia.