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Insulin-Dependent Regulation of Insulin Receptor Concentrations: A Direct Demonstration in Cell Culture

1974; National Academy of Sciences; Volume: 71; Issue: 1 Linguagem: Inglês

10.1073/pnas.71.1.84

1091-6490

James R. Gavin, Jesse Roth, David M. Neville, Pierre De Meyts, Donald N. Buell,

Adipose Tissue and Metabolism

Chronic (5-16 hr) exposure of cultured human lymphocytes to 10 -8 M insulin at 37° in vitro produced a decrease in insulin receptor concentrations unaccounted for by simple occupancy of sites; acute exposure (0-2 hr) was without effect. These results reproduced observations in vivo where chronic hyperinsulinemia (e.g., 10 -8 M insulin in the circulation of obese insulinresistant hyperglycemic mice) is associated with a substantial reduction in the concentration of insulin receptors per cell, while acute hyperinsulinemia in vivo has no effect on receptor concentration. These data suggest a reciprocal relationship between insulin in the extracellular fluid and the concentration of insulin receptors per cell, which is mediated at the target cell itself by intracellular insulin-sensitive regulatory processes and directly affects target-cell sensitivity to hormone.