Tyrosine Kinase Activity of the Insulin Receptor of Patients with Type A Extreme Insulin Resistance: Studies with Circulating Mononuclear Cells and Cultured Lymphocytes

Publisher Website
Google Scholar
Abstract
The syndrome of type A insulin resistance in nonobese women is characterized by hyperinsulinemia, resistance to exogenous insulin, acanthosis nigricans, polycystic ovaries, and masculinization. Insulin binding to intact circulating monocytes and cultured Epstein-Barr virus-transformed B-lymphocytes derived from these patients is decreased in some patients but normal in others. Insulin receptors consist of two subunits; the α-subunit contains the insulin-binding site, and the β-subunit possesses an insulin-sensitive tyrosine-specific protein kinase activity. Insulin binding to circulating monocytes was decreased in five patients, suggesting a decreased number of α-subunits on the surface of cells from the patients with type A insulin resistance. In the present work, we demonstrated that there is a proportional decrease in the function of the β-subunit ($$$i.e. tyrosine kinase activity) in cells from these subjects. In one patient, insulin binding to circulating monocytes was normal, and the insulinstimulated tyrosine kinase activity of the receptors was normal as well. In separate studies, using cultured Epstein-Barr virus-transformed lymphocytes from the same six patients with type A extreme insulin resistance, the results were similar, in that the functions of the α-and β-subunits of the receptor from these cells correlated. Though heterogeneity among the six patients with type A extreme insulin resistance at the level of the kinase activity of their insulin receptors was demonstrated, it does not appear that a selective defect in β-subunit phosphorylation per se can be implicated in the mechanisms of insulin resistance of these patients. These findings are distinct from our previously reported patient with normal binding and very low insulin-stimulated phosphorylation of the β-subunit of the receptor of circulating monocytes, in whom it was speculated that selective reduction in β-subunit phosphorylation was responsible for insulin resistance.

This publication has 20 references indexed in Scilit: