Insulin Receptor Binding and Metabolic Effects of Insulin in Human Subcutaneous Adipose Tissue in Untreated Non-insulin Dependent Diabetes Mellitus

Abstract

Insulin action at the target tissue level in non-insulin dependent diabetes mellitus was investigated using human adipose tissue. Specific adipocyte receptor binding of insulin and the effects of the hormone on glucose oxidation and lipolysis were determined in subcutaneous adipose tissue. The study included 25 patients with untreated non-insulin dependent diabetes mellitus and 38 healthy control subjects matched for age. sex and body weight. Insulin stimulated adipose tissue glucose oxidation in a dose-dependent way in the control subjects. On the other hand, a marked inhibition of this insulin effect was observed in the diabetics. A weak stimulation was observed only at high unphysiological hormone concentrations ≤ 0.7 nmol/l] and the maximal insulin response was 6 times lower than that in the control subjects. However, neither specific insulin receptor binding nor the antilipolytic effect of insulin were inhibited in diabetes. Similar results with insulin binding and the metabolic effects of insulin were obtained in non-obese normoinsulinemic diabetics as compared to moderately obese hyperin-sulinemic diabetics. It is concluded that adipose tissue insulin resistance in non-insulin dependent diabetes mellitus only involves glucose metabolism and not antilipolysis. Furthermore, it may solely be due to postreceptor defects in insulin action and seems not to be influenced by obesity or oversecretion of insulin.