Acanthosis nigricans and obesity: acquired and intrinsic defects in insulin action.

Six obese, severely acanthotic females were evaluated for insulin resistance by an oral glucose tolerance test, intravenous insulin tolerance test, and insulin binding to freshly isolated monocytes, as well as studies of cultured skin fibroblasts. After baseline studies were obtained, the acanthotic subjects were maintained for 14 days on a 500 calorie diet, and the evaluations were repeated. Initial evaluation demonstrated normal glucose tolerance, but marked fasting hyperinsulinemia (57 +/- 5 microU/mL) and dramatically blunted response to exogenous insulin (KITT, 2.0%/min) when compared with five nonacanthotic weight-matched controls (insulin, 15 +/- 2 microU/mL; KITT, 5.2%/min). Monocyte insulin binding for the acanthotic group (0.251 +/- 0.050%/10(6) cells) was only 56% of the binding seen in the obese controls (0.447 +/- 0.108%). After the acanthotic females dieted for 14 days, their hyperinsulinemia and monocyte insulin binding improved, but failed to normalize. The response to exogenous insulin was unchanged and remained drastically blunted. In contrast to the normal insulin binding found in the cultured fibroblasts from the nonacanthotic obese controls, insulin binding to fibroblasts from the acanthotic group was decreased by 40%, suggesting that an intrinsic defect in insulin binding was present. Thus, we conclude that this cohort of acanthotic obese females are considerably more insulin-resistant than nonacanthotic weight-matched females. Furthermore, these studies suggest that the severe insulin resistance results from a combination of an acquired defect related to obesity and an inherent cellular defect in insulin action at, or beyond, the receptor.