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 r eceptor (IR) knockout mice to unravel the metabolic potential of IGF-1 rece ptor (IGF-1R), Both wt and IR-/- myoblasts differentiated into myotubes wit h similar patterns of expression of muscle-specific genes such as MyoD, myo genin and MLC1A indicating that IR is not required for this process. Bindin g of I-125-IGF-1 on wt and IR-/- myotubes was similar showing that IGF-IR w as 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 int o glycogen, induced IRS-1 phosphorylation and activated PI 3-kinase and MAP kinase, two enzymes of major signaling pathways, These effects were compar able to those obtained with wt myotubes using insulin or IGF-1 or with IR-/ - myotubes using insulin at higher concentrations. This study provides a di rect evidence that IGF-1R can represent an alternative receptor for metabol ic signaling in muscle cells. (C) 2001 Federation of European Biochemical S ocieties. Published by Elsevier Science B.V. All rights reserved.