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.

Abstract

We have tested the hypothesis that in vitro exposure of insulin-

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 mellitus

(NIDDM) and nonobese control subjects has been developed.

The adipocytes when cultured in serum-free medium do

not lose their original characteristics in regard to insulin binding

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 exposure

of adipocytes from control subjects decreased basal and

insulin-stimulated glucose transport. The effects of 1 X 1o-7M

insulin were more pronounced than 1 X 10-l' M insulin. Similarly,

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 adipocytes

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 hormonal

factors might be required. Originally published Journal of Clinical Investigation, Vol. 80, No. 4, Oct 1987