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

• Published in: FEBS letters 2001-01, Vol.488 (3), p.174-178
• Main Authors: Baudry, A., Lamothe, B., Bucchini, D., Jami, J., Montarras, D., Pinset, C., Joshi, R.L.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Binding Sites; Biomarkers; Cells, Cultured; Culture Media, Serum-Free; Deoxyglucose; Deoxyglucose - metabolism; Gene Deletion; Glucose; Glucose - metabolism; Glycogen; Glycogen - metabolism; IGF, insulin-like growth factor; IGF-1R, type 1 IGF-1 receptor; Insulin; Insulin - pharmacology; Insulin receptor; Insulin-Like Growth Factor I; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor-1 receptor; IR, insulin receptor; IRS, insulin receptor substrate; Life Sciences; MAP kinase, mitogen-activated protein kinase; Metabolic action; Mice; Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases - metabolism; Muscle cell; Muscle, Skeletal; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Phosphatidylinositol 3-Kinases; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; PI 3-kinase, phosphatidylinositol 3-kinase; Receptor, IGF Type 1; Receptor, IGF Type 1 - metabolism; Receptor, Insulin; Receptor, Insulin - deficiency; Receptor, Insulin - genetics; RNA, Messenger; RNA, Messenger - analysis; RNA, Messenger - genetics; Signal Transduction; Signal Transduction - drug effects
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02435-2

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.