Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.