Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells: effect of differentiation and fusion

R M Palmer, M G Thompson, R M Knott, Gillian Patricia Campbell, A Thom, K S Morrison

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    In proliferating C2C12 myoblasts, serum and physiological concentrations of insulin and IGF-I stimulated protein synthesis and RNA accretion. After fusion, the multinucleated myotubes remained responsive to serum but not to insulin or IGF-I, even though both insulin and type-1 IGF receptor mRNAs increased in abundance. Protein synthetic responses to insulin and IGF-I in myoblasts were not inhibited by dexamethasone, ibuprofen or Ro-31-8220, thus phospholipase A,, cyclo-oxygenase and protein kinase C did not appear to be involved in the signalling mechanisms. Neither apparently were polyphosphoinositide-specific phospholipase C or phospholipase D since neither hormone increased inositol phosphate, phosphatidic acid, choline or phosphatidylbutanol production. Only the phosphatidylinositol-3-kinase inhibitor, wortmannin, and the 70 kDa S6-kinase inhibitor, rapamycin, wholly or partially blocked the effects of insulin and IGF-I on protein synthesis. 2-deoxyglucose uptake remained responsive to insulin and IGF-I after fusion and was also inhibited by wortmannin. The results suggest that the loss of responsiveness after fusion is not due to loss of receptors, but to the uncoupling of a post-receptor pathway, occurring after the divergence of the glucose transport and protein synthesis signalling systems, and that, if wortmannin acts at a single site, this is prior to that point of divergence.

    Original languageEnglish
    Pages (from-to)167-176
    Number of pages10
    JournalBiochimica et Biophysica Acta. Molecular Cell Research
    Issue number2
    Publication statusPublished - 4 Feb 1997


    • insulin
    • insulin-like growth factor I
    • myoblast
    • differentiation
    • intracellular signalling
    • mRNA
    • muscle protein-synthesis
    • skeletal-muscle
    • phosphatidylinositol 3-kinase
    • L6 myoblasts
    • kinase-C
    • glucose-transport
    • factor receptors
    • rat hepatocytes
    • DNA-synthesis
    • stimulation

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