Effect of experimental hyperinsulinemia on insulin binding and glucose transport in isolated rat adipocytes.

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Abstract
The effect of experimental hyperinsulinemia on insulin binding to receptors and cellular sensitivity to insulin action was studied in rat adipocytes. Hyperinsulinemia was induced by injecting NPH [neutral protamine Hagedorn] insulin according to a 14 day gradually increasing dosage schedule. Experimental hyperinsulinemia led to a significant 40% decrease in the number of insulin receptors on isolated adipocytes and a rightward shift in the insulin-glucose transport dose-response curve. This decrease in insulin sensitivity is the predicted functional consequence of a decreased number of insulin receptors. When the effect of insulin on transport was plotted against insulin bound per unit of plasma membrane surface area, the curves from control and hyperinsulinemic rats were superimposable, suggesting normal coupling mechanisms between these 2 processes. When the insulin injections were stopped, insulin receptors and insulin sensitivity rapidly returned to normal. In conclusion, experimental in vivo hyperinsulinemia apparently results in decreased numbers of insulin receptors on target tissues and a corresponding decrease in cellular insulin sensitivity; coupling between insulin receptor complexes and the glucose transport system is probably normal in cells from hyperinsulinemic rats; and these abnormalities are rapidly reversible on insulin withdrawal.