Insulin-like growth factor I circumvents defective insulin action in humanmyotonic dystrophy skeletal muscle cells

Primary human skeletal muscle cell cultures derived from muscles of a myoto nic dystrophy (DM) fetus provided a model in which both resistance to insul in action described in DM patient muscles and the potential ability of insu lin-like growth factor I(IGF-I) to circumvent this defect could be investig ated. Basal glucose uptake was the same in cultured DM cells as in normal m yotubes. In DM cells, a dose of 10 nhl insulin produced no stimulatory effe ct on glucose uptake, and at higher concentrations, stimulation of glucose uptake remained significantly lower than that in normal myotubes. In additi on, basal and insulin-mediated protein synthesis were both significantly re duced compared with those in normal cells. In DM myotubes, insulin receptor messenger RNA expression and insulin receptor binding were significantly d iminished, whereas the expression of GLUT1 and GLUT4 glucose transporters w as not affected. These results indicate that impaired insulin action is ret ained in DM cultured myotubes. The action of recombinant human IGF-I (rhIGF -I) was evaluated in this cellular model. We showed that rhIGF-I is able to stimulate glucose uptake to a similar extent as in control cells and resto re normal protein synthesis level in DM myotubes. Thus, rhIGF-I is able to bypass impaired insulin action in DM myotubes. This provides a solid founda tion for the eventual use of rhIGF-I as an effective treatment of muscle we akness and wasting in DM.