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A B S T R A C T This study examined the relationship between receptor binding of insulin in a metabolically significant target tissue in vitro and sensitivity to insulin in vivo in obese human subjects. Specific insulin binding was measured at 24°C in isolated enlarged fat cells obtained from 16 patients, by observing the effect of increasing concentrations of unlabeled insulin on the binding of [1251]insulin. Scatchard plots of the binding data were curvilinear with an upward concavity, similarly shaped, and essentially parallel. Kinetic studies on the dissociation of [1251]insulin from fat cells indicated that these curvilinear Scatchard plots could be explained by the presence of site:site interactions of the negative cooperative type. Differences in binding between individual patients were predominantly due to differences in the numbers of receptor sites whether expressed in relation to cell number, cell volume, or cell surface area. These findings were not accounted for by differences in [125I]insulin degradation. Acute exposure of adipose tissue to insulin in vitro had no significant effect on [1251]insulin binding to isolated cells. The number of receptor sites was directly correlated with insulin sensitivity in vivo, measured as the rate constant (K111) for the fall in blood glucose after intravenous insulin, and was inversely correlated with the level of fasting plasma insulin. These findings corroborate those from other studies using human mononuclear leukocytes and various tissues from the obese mouse, which indicate that decreased insulin binding is a characteristic feature of insulin resistance in obesity.

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