Acute effects of insulin on skeletal muscle growth and differentiation genes in men with type 2 diabetes

in European Journal of Endocrinology

Correspondence should be addressed to P Dandona; Email: pdandona@KaleidaHealth.org *(S Dhindsa and H Ghanim contributed equally to this work)
Restricted access

Aims

Insulin has anabolic effects on skeletal muscle. However, there is limited understanding of the molecular mechanisms underlying this effect in humans. We evaluated whether the skeletal muscle expression of satellite cell activator fibroblast growth factor 2 (FGF2) and muscle growth and differentiation factors are modulated acutely by insulin during euglycemic–hyperinsulinemic clamp (EHC).

Design and methods

This is a secondary investigation and analysis of samples obtained from a previously completed trial investigating the effect of testosterone replacement in males with hypogonadotropic hypogonadism and type 2 diabetes. Twenty men with type 2 diabetes underwent quadriceps muscle biopsies before and after 4 h of EHC.

Results

The infusion of insulin during EHC raised the expression of myogenic growth factors, myogenin (by 72 ± 20%) and myogenin differentiation protein (MyoD; by 81 ± 22%). Insulin reduced the expression of muscle hypertrophy suppressor, myogenic regulatory factor 4 (MRF4) by 34 ± 14%. In addition, there was an increase in expression of FGF receptor 2, but not FGF2, following EHC. The expression of myostatin did not change.

Conclusions

Insulin has an acute potent effect on expression of genes that can stimulate muscle differentiation and growth.

 

     European Society of Endocrinology

All Time Past Year Past 30 Days
Abstract Views 36 36 36
Full Text Views 6 6 6
PDF Downloads 3 3 3
  • 1

    MandelJLPearsonML. Insulin stimulates myogenesis in a rat myoblast line. Nature 1974 618–620. (https://doi.org/10.1038/251618a0)

  • 2

    ParkSWGoodpasterBHStrotmeyerESde RekeneireNHarrisTBSchwartzAVTylavskyFANewmanAB. Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes 2006 1813–1818. (https://doi.org/10.2337/db05-1183)

    • Search Google Scholar
    • Export Citation
  • 3

    ParkSWGoodpasterBHStrotmeyerESKullerLHBroudeauRKammererCde RekeneireNHarrisTBSchwartzAVTylavskyFA et al. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care 2007 1507–1512. (https://doi.org/10.2337/dc06-2537)

    • Search Google Scholar
    • Export Citation
  • 4

    AbdullaHSmithKAthertonPJIdrisI. Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis. Diabetologia 2016 44–55. (https://doi.org/10.1007/s00125-015-3751-0)

    • Search Google Scholar
    • Export Citation
  • 5

    ZanouNGaillyP. Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways. Cellular and Molecular Life Sciences 2013 4117–4130. (https://doi.org/10.1007/s00018-013-1330-4)

    • Search Google Scholar
    • Export Citation
  • 6

    PawlikowskiBVoglerTOGadekKOlwinBB. Regulation of skeletal muscle stem cells by fibroblast growth factors. Developmental Dynamics 2017 359–367. (https://doi.org/10.1002/dvdy.24495)

    • Search Google Scholar
    • Export Citation
  • 7

    O’ConnorRSPavlathGK. Point:Counterpoint: satellite cell addition is/is not obligatory for skeletal muscle hypertrophy. Journal of Applied Physiology 2007 103 1099–1100. (https://doi.org/10.1152/japplphysiol.00101.2007)

    • Search Google Scholar
    • Export Citation
  • 8

    AlmadaAEWagersAJ. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nature Reviews: Molecular Cell Biology 2016 267–279. (https://doi.org/10.1038/nrm.2016.7)

    • Search Google Scholar
    • Export Citation
  • 9

    EgnerIMBruusgaardJCGundersenK. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle. Development 2016 2898–2906. (https://doi.org/10.1242/dev.134411)

    • Search Google Scholar
    • Export Citation
  • 10

    MorettiICiciliotSDyarKAAbrahamRMurgiaMAgateaLAkimotoTBicciatoSForcatoMPierreP et al. MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity. Nature Communications 2016 12397. (https://doi.org/10.1038/ncomms12397)

    • Search Google Scholar
    • Export Citation
  • 11

    ZammitPS. Function of the myogenic regulatory factors Myf5, MyoD, myogenin and MRF4 in skeletal muscle, satellite cells and regenerative myogenesis. Seminars in Cell and Developmental Biology 2017 19–32. (https://doi.org/10.1016/j.semcdb.2017.11.011)

    • Search Google Scholar
    • Export Citation
  • 12

    GhanimHDhindsaSBatraMGreenKAbuayshehSKuhadiyaNDMakdissiAChaudhuriADandonaP. Effect of testosterone on FGF2, MRF4 and myostatin in hypogonadotropic hypogonadism: relevance to muscle growth. Journal of Clinical Endocrinology and Metabolism 2019 2094–2102. (https://doi.org/10.1210/jc.2018-01832)

    • Search Google Scholar
    • Export Citation
  • 13

    DhindsaSGhanimHBatraMKuhadiyaNDAbuayshehSSandhuSGreenKMakdissiAHejnaJChaudhuriA et al. Insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care 2016 82–91. (https://doi.org/10.2337/dc15-1518)

    • Search Google Scholar
    • Export Citation
  • 14

    SharmaMMcFarlaneCKambadurRKukretiHBonalaSSrinivasanS. Myostatin: expanding horizons. IUBMB Life 2015 589–600. (https://doi.org/10.1002/iub.1392)

    • Search Google Scholar
    • Export Citation
  • 15

    LitwiniukAPijetBPijet-KucickaMGajewskaMPajakBOrzechowskiA. FOXO1 and GSK-3beta are main targets of insulin-mediated myogenesis in C2C12 muscle cells. PLoS ONE 2016 e0146726. (https://doi.org/10.1371/journal.pone.0146726)

    • Search Google Scholar
    • Export Citation
  • 16

    PopeJr HGWoodRIRogolANybergFBowersLBhasinS. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocrine Reviews 2014 341–375. (https://doi.org/10.1210/er.2013-1058)

    • Search Google Scholar
    • Export Citation
  • 17

    IpEJBarnettMJTenerowiczMJPerryPJ. Weightlifting’s risky new trend: a case series of 41 insulin users. Current Sports Medicine Reports 2012 176–179. (https://doi.org/10.1249/JSR.0b013e31825da97f)

    • Search Google Scholar
    • Export Citation