Type II Diabetes and Insulin Resistance: Evidence for Lack of Inherent Cellular Defects in Insulin Sensitivity

To determine if inherent cellular differences in insulin sensitivity account for the insulin resistance of non-insulin- dependent diabetes, the effect of insulin on several aspects of cell glucose metabolism was compared in fibroblasts from diabetics and matched nondiabetic controls. The response of total cell glucose metabolism to insulin was assessed by measurement of 14C-glucose uptake. Insulin stimulated cell glucose incorporation in nondiabetic cells up to twofold with half-maximal stimulation at approximately 3 × 10-9M insulin. This was similar to that observed in diabetic cells. Insulin stimulation of I glycogen synthase activity was also compared in the cells from diabetics and nondiabetics. Both groups demonstrated a threefold increase in %I activity in the presence of insulin with half-maximal stimulation at approximately 2 × 10∼9 M. There were no differences between diabetics and nondiabetics in either magnitude of response or insulin concentration for half-maximal stimulation. Finally, insulin stimulation of hexose transport was compared in the two cell types using 2-deoxyglucose. In both groups hexose transport was elevated approximately 40% over baseline in the fibroblast in the presence of insulin, with half-maximal stimulation at approximately 2 × 10-9 M insulin. No differences were found in insulin action on glucose metabolism in fibroblasts from diabetics and nondiabetics; these results may indicate that there are no inherent differences in cell sensitivity to insulin's glucoregulatory action in non-insulin-dependent diabetics.

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