Long-term effect of insulin on glucose transport and insulin binding in cultured adipocytes from normal and obese humans with and without non-insulin-dependent diabetes.

We have tested the hypothesis that in vitro exposure of insu- lin-resistant adipocytes with insulin results in improved insulin action. A primary culture system of adipocytes from obese subjects with or without non-insulin-dependent diabetes mel- litus (NIDDM) and nonobese control subjects has been devel- oped. The adipocytes when cultured in serum-free medium do not lose their original characteristics in regard to insulin bind- ing and glucose transport. The adipocytes from three groups were incubated with insulin (0, 10-10 M, and lo-7 M) for 24 h at 370C, receptor-bound insuMin was dissociated, and basal and insulin (1 X 10-11_10-7 M)-stimulated glucose transport and "2I-insulin binding were determined. The 24-h insulin expo- sure of adipocytes from control subjects decreased basal and insulin-stimulated glucose transport. The effects of 1 X 1o-7 M insulin were more pronounced than 1 X 10-l' M insulin. Simi- larly, insulin exposure decreased insulin sensitivity and responsiveness of cultured adipocytes from obese and NIDDM patients. The insulin-induced reduction in insulin sensitivity and responsiveness for glucose transport in three groups were due to alterations at insulin binding and postbinding levels. In conclusion, insulin induces insulin resistance in control adipo- cytes and further worsens the insulin resistance of adipocytes from obese and NIDDM subjects. For insulin to improve the insulin resistance of adipocytes from NIDDM patients, either more prolonged in vitro insulin exposure and/or other hor- monal factors might be required.