RAD - A MEMBER OF THE RAS FAMILY OVEREXPRESSED IN MUSCLE OF TYPE-II DIABETIC HUMANS

To identify the gene or genes associated with insulin resistance in Ty pe II (non-insulin-dependent) diabetes mellitus, subtraction libraries were prepared from skeletal muscle of normal and diabetic humans and screened with subtracted probes. Only one clone out of 4000 was select ively overexpressed in Type II diabetic muscle as compared to muscle o f non-diabetic or Type I diabetic individuals. This clone encoded a ne w 29-kilodalton member of the Ras-guanosine triphosphatase superfamily and was termed Rad (Ras associated with diabetes). Messenger ribonucl eic acid of Rad was expressed primarily in skeletal and cardiac muscle and was increased an average of 8.6-fold in the muscle of Type II dia betics as compared to normal individuals.