IGF-1 receptor as an alternative receptor for metabolic signaling in insulin receptor-deficient muscle cells

We have derived skeletal muscle cell lines from wildtype (wt) and insulin receptor (IR) knockout mice to unravel the metabolic potential of IGF-1 receptor (IGF-1R), Both wt and IR-/- myoblasts differentiated into myotubes with similar patterns of expression of muscle-specific genes such as MyoD, myogenin and MLC1A indicating that IR is not required for this process. Binding of I-125-IGF-1 on wt and IR-/- myotubes was similar showing that IGF-IR was not upregulated in the absence of IR, Stimulation of IR-/- myotubes with IGF-1 (10(-10) to 10(-7) M) increased glucose uptake and incorporation into glycogen, induced IRS-1 phosphorylation and activated PI 3-kinase and MAP kinase, two enzymes of major signaling pathways, These effects were comparable to those obtained with wt myotubes using insulin or IGF-1 or with IR-/- myotubes using insulin at higher concentrations. This study provides a direct evidence that IGF-1R can represent an alternative receptor for metabolic signaling in muscle cells. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.