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.
Baudry
A
A
Department of Genetics, ICGM, INSERM U257, Paris, France.
Lamothe
B
B
Bucchini
D
D
Jami
J
J
Montarras
D
D
Pinset
C
C
Joshi
R L
RL
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D015415:Biomarkers; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003847:Deoxyglucose / Q000378:metabolism; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011972:Receptor, Insulin / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D015415:Biomarkers; D016895:Culture Media, Serum-Free; D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose