Characterization of insulin-like actions of anti-insulin receptor antibodies. Effects on insulin binding, insulin degradation, and glycogen synthesis in isolated rat hepatocytes.

Abstract

The insulin-like properties of anti-insulin receptor antibodies isolated from the serum of a patient with insulin-resistant diabetes were studied with the use of isolated rat hepatocytes.Whole patient serum inhibited '261-insulin binding to hepatocytes; half-maximal inhibition occurred at a serum dilution of 1:80.IgG and its divalent peptic (F(ab)z) and univalent (Fab') Fab fragments possessed all of the inhibitory activity found in serum.Antireceptor serum, as well as IgG, (Fab)z, and Fab', inhibited degradation of 1261-insulin by hepatocytes to an extent equal to its inhibition of insulin binding.This observation is consistent with our previous demonstration that receptor-bound insulin is the substrate for insulin degradation in these cells (Terris,