LAUSR

Introduction: Chronic hyperglycemia injures both micro-and microvasculature. Conversely, insulin stimulates vascular nitric oxide production and acts as a vasodilator. Whether acute hyperglycemia (AH) inhibits insulin’s vasodilator action in healthy vasculature is unknown. Here we tested whether AH interfered with insulin’s action to recruit microvasculature, enhance endothelial function, or diminish vascular stiffness. Methods: Nine healthy, fasting subjects (ages 18-35 years; BMI 18-25 kg/m 2 ) twice received a 1 mU/kg/minute 2-hour insulin clamp. On one occasion, subjects were euglycemic (EH); and on the second, were hyperglycemic (∼200 mg/dL) (HH) for 2 hours before and throughout the clamp. Octreotide infusion blocked endogenous insulin in both studies. We assessed endothelial function by flow-mediated dilation (FMD) and arterial stiffness with pulse wave velocity (PWV) and augmentation index (AI). We used contrast-enhanced ultrasound to measure insulin-mediated capillary recruitment in skeletal and cardiac muscle. Linear mixed model was used for statistical analysis, with Bonferroni correction for comparison between studies. Results: Insulin increased carotid-femoral PWV (p=0.02 for Δ PWV) but decreased AI (p= 0.02) during HH, with AI significantly reduced in HH compared to EH (p=0.04). Insulin recruited microvasculature (p Discussion: This study provides evidence that 4 hours of AH evokes insulin-induced increases of carotid-femoral arterial stiffness in healthy subjects. Insulin’s ability to recruit microvasculature is preserved during AH. Disclosure W.B. Horton: None. L. Jahn: None. L. Hartline: None. J.T. Patrie: None. E. Barrett: Research Support; Self; AstraZeneca. Funding National Institutes of Health (F32HL142304-01)