Effect of Persistent Mild Hyperglycemic Hyperinsulinemia on Development of Insulin Resistance in Rats

Abstract

The effect of persistant mild hyperglycemic hyperinsulinemia on the development of the insulin resistance in rats was studied in vivo. Also, the characteristics of the insulin resistance compared with the insulin resistance of STZ diabetic rats. Persistant mild hyperglycemic hyperinsulinemic rat model was produced by ingestion of glucose polymer for 8 days. The glucose disappearance and infusion rate was measured by hyperinsulinemic euglycemic clamp technique at steady state of blood glucose and insulin levels. The clamped level of blood glucose was 100 mg/dl, and the clamped levels of insulin were (physiologic condition) and (supramaximal condition). Hepatic glucose producticon rate was calculated using measured data. And the glycogen synthetic capacity of skeletal muscle(soleus) and liver was measured after 2 hours of hyperinsulinemic euglycemic clamp study. The glucose disappearance and glucose infusion rate in glucose polymer group was decreased in the both physiological and supramaximal insulin level compared to the rate of the normal control group. The rate of STZ diabetic group wase lowest at supramaximal insulin level among two another experimental groups. The hepatic glucose production rate of glucose polymer group was decreased compared to normal control but increased in STZ diabetic group. The glycogen synthetic capacity of skeletal muscle and liver of glucose polymer group was not significantly different from normal control group, but it was markdly decreased in STZ diabetic group. These results suggest that persistant mild hyperglycemic hyperinsulinemia may induce insulin resistance, but glycogen synthetic capacity is intact.