Increased IGFR activity and glucose transport in cultured skeletal muscle from insulin receptor null mice

We have studied the role of the insulin receptor (IR) in metabolic and grow th-promoting effects of insulin on primary cultures of skeletal muscle deri ved from the limb muscle of IR null mice. Cultures of IR null skeletal musc le displayed normal morphology and spontaneous contractile activity. Expres sion of muscle-differentiating proteins was slightly reduced in myoblasts a nd myotubes of the IR null skeletal muscle cells, whereas that of the Na+/K + pump appeared to be unchanged. Insulin-like growth factor receptor (IGFR) expression was higher in myoblasts from IR knockout (IRKO) than from IR wi ld-type (IRWT) mice but was essentially unchanged in myotubes. Expression o f the GLUT-1 and GLUT-4 transporters appeared to be higher in IRKO than in IRWT myoblasts and was significantly greater in myotubes from IRKO than fro m IRWT cultures. Consistent with GLUT expression, both basal and insulin or insulin-like growth factor I (IGF-I)-stimulated glucose uptakes were highe r in IR null skeletal myotubes than in wild-type skeletal myotubes. Interes tingly, autophosphorylation of IGFR induced by insulin and IGF-I was marked ly increased in IR null skeletal myotubes. These results indicate that, in the absence of IR, there is a compensatory increase in basal as well as in insulin- and IGF-I-induced glucose transport, the former being mediated via increased activation of the IGF-I receptor.