Moderate increases in dietary fat impair microvascular but not myocyte actions of insulin in skeletal muscle of Sprague Dawley rats

Abstract

Enhanced microvascular perfusion in skeletal muscle is important for insulin‐mediated glucose disposal. We have previously demonstrated that high fat‐fed rats (36% fat wt/wt, 4 weeks) have impaired insulin‐stimulated microvascular perfusion and reduced insulin‐stimulated muscle glucose uptake (IMGU). We hypothesised that moderate increases in dietary fat might impair microvascular responses without altering myocyte insulin sensitivity. Rats were fed 5% (5%FD) or 9% (9%FD) fat (wt/wt) diets. After 4 weeks anesthetized rats were subjected to either a hyperinsulinemic euglycemic clamp, and microvascular perfusion measured from hindleg disappearance of 1‐methylxanthine, or pump‐perfusion of the isolated rat hindlimb, which allows myocyte insulin responses to be measured in the absence of altered perfusion. Body weight, epididymal fat pad weight, and fasting plasma glucose were not altered by the diets. Fasting plasma insulin concentrations were moderately elevated, and plasma free fatty acid concentrations were significantly increased in 9%FD. Glucose infusion rate, IMGU and microvascular perfusion during the clamp were significantly impaired in 9%FD. In contrast, IMGU in the isolated, perfused hindlimb was unaltered by diet. These data show that increased dietary fat impairs microvascular insulin responses before those of skeletal myocytes, but still leads to muscle insulin resistance in vivo.