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.