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

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    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
    Volume1355
    Issue number2
    DOIs
    Publication statusPublished - 4 Feb 1997

    Keywords

    • 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

    Cite this

    Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells : effect of differentiation and fusion . / Palmer, R M ; Thompson, M G ; Knott, R M ; Campbell, Gillian Patricia; Thom, A ; Morrison, K S .

    In: Biochimica et Biophysica Acta. Molecular Cell Research, Vol. 1355, No. 2, 04.02.1997, p. 167-176.

    Research output: Contribution to journalArticle

    Palmer, R M ; Thompson, M G ; Knott, R M ; Campbell, Gillian Patricia ; Thom, A ; Morrison, K S . / Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells : effect of differentiation and fusion . In: Biochimica et Biophysica Acta. Molecular Cell Research. 1997 ; Vol. 1355, No. 2. pp. 167-176.
    @article{7734ac021953425aac7fe41f9915c3c9,
    title = "Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells: effect of differentiation and fusion",
    abstract = "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.",
    keywords = "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",
    author = "Palmer, {R M} and Thompson, {M G} and Knott, {R M} and Campbell, {Gillian Patricia} and A Thom and Morrison, {K S}",
    year = "1997",
    month = "2",
    day = "4",
    doi = "10.1016/S0167-4889(96)00127-9 |",
    language = "English",
    volume = "1355",
    pages = "167--176",
    journal = "Biochimica et Biophysica Acta. Molecular Cell Research",
    issn = "0167-4889",
    publisher = "Elsevier",
    number = "2",

    }

    TY - JOUR

    T1 - Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells

    T2 - effect of differentiation and fusion

    AU - Palmer, R M

    AU - Thompson, M G

    AU - Knott, R M

    AU - Campbell, Gillian Patricia

    AU - Thom, A

    AU - Morrison, K S

    PY - 1997/2/4

    Y1 - 1997/2/4

    N2 - 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.

    AB - 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.

    KW - insulin

    KW - insulin-like growth factor I

    KW - myoblast

    KW - differentiation

    KW - intracellular signalling

    KW - mRNA

    KW - muscle protein-synthesis

    KW - skeletal-muscle

    KW - phosphatidylinositol 3-kinase

    KW - L6 myoblasts

    KW - kinase-C

    KW - glucose-transport

    KW - factor receptors

    KW - rat hepatocytes

    KW - DNA-synthesis

    KW - stimulation

    U2 - 10.1016/S0167-4889(96)00127-9 |

    DO - 10.1016/S0167-4889(96)00127-9 |

    M3 - Article

    VL - 1355

    SP - 167

    EP - 176

    JO - Biochimica et Biophysica Acta. Molecular Cell Research

    JF - Biochimica et Biophysica Acta. Molecular Cell Research

    SN - 0167-4889

    IS - 2

    ER -