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

We have derived skeletal muscle cell lines from wild-type (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 ¹²⁵I-IGF-1 on wt and IR^-/- myotubes was similar showing that IGF-1R 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.