The T lymphocyte insulin receptor in diabetes and obesity. An intrinsic binding defect

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 and 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 x 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 nonobese group. In contrast, binding was reduced to 1.23 ± 0.05 x 10^-21 mol/cell in 11 obese subjects (38 yr, 143 ± 5% fat) and even further to 1.0 ± 0.06 x 10