Glucose transport and metabolism in adipocytes from newly diagnosed untreated insulin-dependent diabetics. Severely impaired basal and postinsulin binding activities

Abstract

Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.