Impaired insulin‐mediated vasodilation may contribute to hyperglycemia following high fat intake (1030.1)

Abstract

Impaired insulin‐mediated vasodilation may contribute to hyperglycemia following high fat intake Ricklefs Ka, Simperova Ab, Reaven Pc, Sands Mc, Sweazea KLa,b aSchool of Nutrition and Health Promotion, bSchool of Life Sciences, Arizona State University; cCarl T. Hayden Veterans Affairs Medical Center, Phoenix, AZThe incidence of type 2 diabetes (T2D) worldwide has increased markedly and constitutes one of the major threats to global health. Insulin resistance is a major factor in the pathogenesis of T2D. We have previously shown that feeding rats a high fat diet (HFD) results in increased adiposity as well as the development of mild hyperglycemia, insulin resistance, and impaired vasodilation, all major risk factors for T2D and cardiovascular disease. While insulin sensitivity has been studied extensively in skeletal muscle, the potential impacts of HFD and impaired insulin signaling in the vasculature are less known. Additionally, impaired insulin‐mediated vasodilation may contribute to reduced postprandial tissue perfusion thereby diminishing glucose uptake. The purpose of this study was to explore the effects of a HFD on the insulin‐mediated vasodilatory pathway (i.e., IRS‐1, PI3K, Akt, and eNOS) in isolated aortas from male Sprague‐Dawley rats fed a 60% HFD for 6 weeks versus rats fed standard rodent chow (5% fat). Western blot analyses indicate that protein expression of IRS‐1 and Akt, and phosphorylation of Akt(t306 and s473) were not significantly affected by HFD. In contrast, p‐IRS‐1 and p‐PI3K(p55) protein expression were significantly diminished (p=0.016 and 0.045, respectively) in HFD aortas compared to chow‐fed controls. These results suggest that endothelial dysfunction and hyperglycemia observed in these HFD rats may be attributed in part to reduced expression of insulin signaling pathway intermediates.