Js. Moyers et al., OVEREXPRESSION OF RAD INHIBITS GLUCOSE-UPTAKE IN CULTURED MUSCLE AND FAT-CELLS, The Journal of biological chemistry, 271(38), 1996, pp. 23111-23116
Rad is a Ras-like GTPase that was isolated by subtraction cloning of h
uman muscle and shown to have increased expression in some individuals
with Type II diabetes, To ascertain the potential role of Rad in insu
lin-mediated signaling, we have overexpressed Rad in myocyte and adipo
cyte cell lines, Expression of Rad resulted in a 50-90% reduction in i
nsulin-stimulated 2-deoxyglucose glucose uptake in C2C12 murine myotub
es, L6 rat myotubes, and 3T3-L1 adipocytes and a 25% reduction in 3-O-
methylglucose uptake in 3T3-L1 adipocytes, This occurred despite unalt
ered levels of glucose transporter expression, with no detectable chan
ge in Glut4 translocation and with no alteration in insulin receptor o
r substrate phosphorylation or phosphatidylinositol 3-kinase activity,
These data indicate that Rad is a negative regulator of glucose uptak
e and that this effect may be due to a decrease in the intrinsic activ
ity of the transporter molecules, rather than an effect on the translo
cation of Glut4.