Phosphorylation Of The Insulin Receptor By Immunoglobulin G In A Patient With Type B Insulin Resistance

We have an opportunity to examine a female patient with type B insulin resistance manifested by acanthosis nigricans, hyperinsulinemia and circulating anti-insulin receptor antibodies. In spite of the severe insulin resistance, fasting hypoglycemia was occasionally shown during her admission. Patient's immunoglobulin G (B-IgG) purified by protein A sepharose column inhibited to insulin binding to IM9 lymphocytes up to 5%. In contrast, 6.2 CIM B-IgG stimulated 2DG incorporation at about 3.4 fold over basal in CHO-hIR cells overexpressing human insulin receptor. Immunoblotting analysis showed that 95 kDa protein was tyrosine-phosphorylated by the treatment with B-IBG for 5 min in CHO-hIR cells, suggesting B-IgG may have potential to induce the insulin receptor autophosphorylation. Contrary, the treatment of CHO-hIGFIR with B-IgG did not show any visible tyrosine phosphorylated protein. Taken together, IgG from the patient studied here may have the ability to evoke insulin signal transduction through the insulin receptor which would be associated with fasting hypoglycemia.