MEMBRANE GLYCOPROTEIN PC-1 AND INSULIN-RESISTANCE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

MOST patients with non-insulin-dependent diabetes mellitus are resista nt to both endogenous and exogenous insulin(1). Insulin resistance pre cedes the onset of this disease(2-4), suggesting that it may be an ini tial abnormality. Insulin-receptor kinase activity is impaired in musc le, fibroblasts and other tissues of many patients with non-insulin-de pendent diabetes mellitus(5), but abnormalities in the insulin-recepto r gene do not appear to be the cause of this decreased kinase activity (6,7). Skin fibroblasts from certain insulin-resistant patients contai n an inhibitor of insulin-receptor tyrosine kinase(8,9). Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10,1 1). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells red uces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non- insulin-dependent diabetes mellitus.