Insulin receptors of cultured human lymphocytes (IM-9). Lack of receptor-mediated degradation.

The binding of insulin to cultured human lymphocytes of the IM-9 line was investigated at near-physiological conditions, i.e. 37 degrees C, pH 7.4, using a monoiodinated insulin exclusively labeled in tyrosyl residue 14 of the A chain. Although the apparent dissociation constant did not differ much from that found in rat adipocytes, the rate constants were about 1 order of magnitude greater. The rate of dissociation of 60 pM of labeled insulin was accelerated more in the lymphocytes than in adipocytes by the addition of 50 nM insulin to the wash-out medium. In rat adipocytes insulin is degraded both by receptor-independent and receptor-mediated processes (Gliemann, J., and Sonne, O. (1978) J. Biol. Chem. 253, 7857-7863). Lymphocytes possessed a receptor-independent insulin-degrading system with the same properties as that of adipocytes. However, receptor-mediated degradation was absent and insulin binding is therefore a true reversible process. The following is concluded: 1) The binding sites of the receptors in IM-9 lymphocytes are different from those of the insulin-responsive adipocytes and hepatocytes. 2) The lymphocytes lack the enzyme responsible for the receptor-mediated degradation or a coupling factor between the receptor and the enzyme.