AUTOPHOSPHORYLATION OF INSULIN-RECEPTOR IN A PATIENT WITH WERNERS-SYNDROME ASSOCIATED WITH INSULIN-RESISTANT DIABETES-MELLITUS

The tissue sensitivity to insulin was evaluated using the hyperinsulin emic euglycemic clamp technique in a 44-year old male with Werner's sy ndrome associated with diabetes mellitus. In addition, the autophospho rylation of insulin receptors and the number of autophosphorylated ins ulin receptors were measured in his erythrocytes by a new enzyme-linke d immunosorbent assay. He had an increased serum insulin level (30.5 m u U/ml) in addition to hyperglycemia (226 mg/dl), suggesting that he h ad insulin-resistant diabetes mellitus. A clamp study revealed that hi s insulin-stimulated glucose disposal rate (2.80 mg/kg/min) was compar able to that in noninsulin-dependent diabetes mellitus (4.14 +/- 1.94 (SD) mg/kg/min, n=23). The number of autophosphorylated insulin recept ors per 300 mu l of erythrocytes was also identical to that in normal control subjects. In addition, the autophosphorylation of insulin rece ptors determined at six different insulin concentrations was within th e normal range, even when it was expressed as per 300 mu l of erythroc ytes as well as per unit receptor. These results demonstrate that insu lin resistance in the patient with Werner's syndrome is caused by a de fect that cannot be detected by means employed in this study, and sugg est that the defect is present at the steps distal to the autophosphor ylation of tyrosine kinase of insulin receptors.