Altered Insulin Binding to Monocytes and Diploid Fibroblasts from Obese Donors*

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Abstract
Insulin binding was studied in fibroblasts and monocytes from nondiabetic subjects with a range of body mass indices (BMI). Binding was compared in fibroblasts from extremely obese subjects and normal weight subjects. The [125I] insulin displacement curve for the obese subjects was shifted to the right. Scatchard analysis suggested that cells from the obese group have an increased number of receptors with decreased affinity. Significant correlations were observed between the cell donor’s BMI and the concentration of insulin required to inhibit half of the [125I]insulin specifically bound to fibroblasts (r = 0.8; P < 0.005), the high affinity dissociation constant (r = 0.8; P < 0.005), and the number of receptors (r = 0.6; P < 0.05). Insulin binding to monocytes was measured for nondiabetic Pima Indian subjects with a range of BMI values. Scatchard analysis of the data indicated that the high affinity dissociation constant was positively correlated with BMI (r = 0.6; P < 0.02). The number of receptors was also positively correlated with BMI (r = 0.6; P < 0.05). The observation that both cultured cells and monocytes exhibit changes in insulin binding that correlate with the obesity of the cell source suggests that the insulin resistance of obesity may be partially a reflection of genetic differences at the site of the insulin receptor.