Based on in vitro studies of insulin receptors in a variety of tissues, it was postulated that circulating insulin levels govern receptor number in vivo ahd that the insulin resistance characteristic of adult-onset diabetics is the consequence of reduced receptor numbers secondary to hyperinsulinemia. The quiescent T lymphocyte in vivo uniquely does not bear a receptor for insulin. The receptor appears after activation by a mitogen or antigen. Thus, free from the influence of endogenous insulin levels, this cell is an excellent model to study the intrinsic relations between diabetes and the insulin receptor. Specific binding to T cells activated by lectin in culture from 20 juvenile-onset diabetics (26 yr, 109 ± 5% fat) was 1.52 ± 0.08 × 10−21 mol/cell, no different from the 1.55 ± 0.08 in 20 normal subjects (20 yr, 100 ± 3% fat) or than in an aged non-obese group. In contrast, binding was reduced to 1.23 ± 0.05 × 10−21 mol/cell in 11 obese subjects (38 yr, 143 ± 5% fat) and even further to 1.0 ± 0.06 × 10−21 mol/cell in 21 adult-onset diabetics (53 yr, 160 ± 10% fat). The appearance of the insulin receptor on cultured stimulated T cells was analyzed by Scatchard plots, which demonstrated that receptor affinity was normal (Kd = 3−5 nM) but the receptor number was distinctly fewer (6131 ± 465 vs 2904 ± 172 sites/cell). In summary, these data show that (1) T lymphocyte insulin receptor characteristics are normal in juvenile-onset diabetics and in elderly nonobese subjects, (2) obesity itself reduces insulin receptor numbers, (3) insulin receptor binding in adult-onset diabetics is significantly less than in. obese controls and represents a defect in receptor number unrelated to in vivo insulin concentrations. We conclude that, in both obesity and adult-onset diabetes, a reduction in T cell insulin receptors is produced by a novel mechanism not attributable to classic ligand-receptor interactions.

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