Effects of hyperinsulinemia on glucose and lipid transporter expression in insulin-sensitive horses.

Abstract: Plasma insulin concentrations are elevated (hyperinsulinemia) in horses with obesity-associated insulin resistance. In other species, insulin resistance is partly due to reduced levels of insulin receptor and the insulin-sensitive glucose transporter, and, in vitro, chronic hyperinsulinemic conditions reduce the expression of these proteins. Consumption of grain-based concentrate feeds results in postprandial hyperinsulinemia in horses, and adaptation to these diets is associated with insulin resistance. As such, it is possible that the repeated, chronic postprandial hyperinsulinemia associated with these diets could contribute to the development of insulin resistance. The purpose of the current study was to investigate the influence of a 6-h insulin infusion that increased plasma insulin concentrations to >1,000 mIU/L, on the expression of insulin receptor and glucose and lipid transporters in skeletal muscle and adipose tissue of lean, insulin-sensitive horses. Insulin infusion decreased transcript abundance of the glucose transporter 4 (P<0.05), glucose transporter 1 (GLUT1; P<0.09), and the insulin receptor (P<0.001) in adipose tissue, while increasing transcript abundance of GLUT1 (P<0.09) and decreasing protein abundance of the insulin receptor (P<0.09) in skeletal muscle. The acute, 6 hyperinsulinemic conditions achieved in this experiment resulted in alterations to mechanisms of glucose transport that could promote insulin resistance via reduced insulin-stimulated glucose disposal. Insulin infusion also reduced transcript abundance of the lipid transporters CD36 (P<0.001) and fatty acid transporter protein (FATP; P<0.05) in adipose tissue while increasing FATP (P<0.05) and lipoprotein lipase (P<0.01) in skeletal muscle. The reduction in adipose tissue lipid transporters could have been due to the decreased plasma lipid concentrations, whereas the increase in skeletal muscle may indicate that insulin stimulates lipid uptake into equine skeletal muscle. This report provides preliminary evidence that severe hyperinsulinemia alters glucose and lipid transporter expression that could promote an insulin-resistant state; these should be further investigated in horses consuming grain-based concentrates.