Muscle insulin resistance resulting from impaired microvascular insulin sensitivity in Sprague Dawley rats

Enhanced microvascular perfusion of skeletal muscle is important for nutrient exchange and contributes ∼40% insulin-mediated muscle glucose disposal. High fat-fed (36% fat wt./wt.) rats are a commonly used model of insulin-resistance that exhibit impairment of insulin-mediated microvascular recruitment and muscle glucose uptake, which is accompanied by myocyte insulin-resistance. Distinguishing the contribution of impaired microvascular recruitment and impaired insulin action in the myocyte to decreased muscle glucose uptake in these high-fat models is difficult. It is unclear whether microvascular and myocyte insulin-resistance develop simultaneously. To assess this, we used a rat diet model with a moderate increase (two-fold) in dietary fat.