The present work has concentrated primarily on studying the tyrosine kinase activity of the insulin receptor. In previous studies of a mutant cell line from an insulin resistant patient, a defect in tyrosine kinase activity in the monocytes was demonstrated. A similar defect can be shown in erythrocytes and fibroblasts and repair of this defect can be found in EBV-transformed lymphocytes from the patient. In contrast, most patients with Type A syndrome with insulin resistance and low binding have concomitantly low tyrosine kinase activity. A new method has been developed to study red blood cell tyrosine kinase activity of the insulin receptor. A defect in Type II diabetes can be shown. Studies are underway to determine the effects of fasting, diet and treatment on this defect. Diacylglycerol, a phorbol ester, also inhibits insulin binding to cultured cells and blood monocytes. Further these tumor-promoting agents cause a complex-type of phosphorylation of the insulin receptor.
