Skip to main content
SpringerLink
Log in

Exercise reduces cellular stress related to skeletal muscle insulin resistance

  • Original Paper
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

This study sought to evaluate the effects of a single session of exercise on the expression of Hsp70, of c-jun N-terminal kinase (JNK), and insulin receptor substrate 1 serine 612 (IRSser612) phosphorylation in the skeletal muscle of obese and obese insulin-resistant patients. Twenty-seven volunteers were divided into three experimental groups (eutrophic insulin-sensitive, obese insulin-sensitive, and obese insulin-resistant) according to their body mass index and the presence of insulin resistance. The volunteers performed 60 min of aerobic exercise on a cycle ergometer at 60 % of peak oxygen consumption. M. vastus lateralis samples were obtained before and after exercise. The protein expressions were evaluated by Western blot. Our findings show that compared with paired eutrophic controls, obese subjects have higher basal levels of p-JNK (100 ± 23 % vs. 227 ± 67 %, p = 0.03) and p-IRS-1ser612 (100 ± 23 % vs. 340 ± 67 %, p < 0.001) and reduced HSP70 (100 ± 16 % vs. 63 ± 12 %, p < 0.001). The presence of insulin resistance results in a further increase in p-JNK (460 ± 107 %, p < 0.001) and a decrease in Hsp70 (46 ± 5 %, p = 0.006), but p-IRS-1ser612 levels did not differ from obese subjects (312 ± 73 %, p > 0.05). Exercise reduced p-JNK in obese insulin-resistant subjects (328 ± 33 %, p = 0.001), but not in controls or obese subjects. Furthermore, exercise reduced p-IRS-1ser612 for both obese (122 ± 44 %) and obese insulin-resistant (185 ± 36 %) subjects. A main effect of exercise was observed in HSP70 (p = 0.007). We demonstrated that a single session of exercise promotes changes that characterize a reduction in cellular stress that may contribute to exercise-induced increase in insulin sensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aguirre V, Uchida T, Yenush L, Davis R, White MF (2000) The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 275:9047–9054

    Article  CAS  PubMed  Google Scholar 

  • Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM (2005) Increased p85/55/50 expression and decreased phosphatidylinositol 3-kinase activity in insulin-resistant human skeletal muscle. Diabetes 54:2351–2359

    Article  CAS  PubMed  Google Scholar 

  • Bergström J, Hultman E (1966) Muscle glycogen synthesis after exercise: an enhancing factor localized to the muscle cells in man. Nature London 210:309–310

    Article  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Brazilian Ministry of Health. Vigitel Brazil 2010: surveillance of risk and protective factors for chronic diseases through telephone survey. Brasilia: Office of Strategic and Participative Management, Bureau of Health Surveillance, Ministry of Health, 2011. p. 37

  • Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Mandarino LJ (2003) Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action. J Appl Physiol 95:2519–2529

    CAS  PubMed  Google Scholar 

  • Chung J, Nguyen AK, Henstridge DC, Holmes AG, Chan MH, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy SJ, Horvath I, Mestril R, Watt MJ, Hooper PL, Kingwell BA, Vigh L, Hevener A, Febbraio MA (2008) HSP72 protects against obesity-induced insulin resistance. PNAS 105:1739–1744

    Article  CAS  PubMed  Google Scholar 

  • Colditz GA, Willett WC, Stampfer MJ, Manson JE, Hennekens CH, Arky RA, Speizer FE (1990) Weight as a risk factor for clinical diabetes in women. Am J Epidemiol 132:501–513

    CAS  PubMed  Google Scholar 

  • Daviau A, Proulx R, Robitaille K, Di Fruscio M, Tanguay RM, Landry J, Patterson C, Durocher Y, Blouin R (2006) Down-regulation of the mixed-lineage dual leucine zipper-bearing kinase by heat shock protein 70 and its co-chaperone CHIP. J Biol Chem 281:31467–31477

    Article  CAS  PubMed  Google Scholar 

  • Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252

    Article  CAS  PubMed  Google Scholar 

  • De Fea K, Roth RA (1997) Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Biochemistry 36:12939–12947

    Article  PubMed  Google Scholar 

  • Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M (2011) National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377:557–567

    Article  PubMed  Google Scholar 

  • Garetto LP, Richter EA, Goodman MN, Ruderman NB (1984) Enhanced muscle glucose metabolism after exercise in the rat: the two phases. Am J Physiol Endocrinol Metab 246:E471–E475

    CAS  Google Scholar 

  • Geiger PC, Gupte AA (2011) Heat shock proteins are important mediators of skeletal muscle insulin sensitivity. Exerc Sport Sci Rev 39:34–42

    Article  PubMed Central  PubMed  Google Scholar 

  • Geloneze B, Repetto EM, Geloneze SR, Tambascia MA, Ermetice MN (2006) The threshold value for insulin resistance (HOMAIR) in an admixtured population IR in the Brazilian Metabolic Syndrome Study. Diabetes Res Clin Pract 72:219–220

    Article  CAS  PubMed  Google Scholar 

  • Gupte AA, Bomhoff GL, Swerdlow RH, Geiger PC (2009) Heat treatment improves glucose tolerance and prevents skeletal muscle insulin resistance in rats fed a high-fat diet. Diabetes 58:567–578

    Article  PubMed  Google Scholar 

  • Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kline MP, Morimoto RI (1997) Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol 17:2107–2115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kurucz I, Morva A, Vaag A, Eriksson K, Huang X, Groop L, Koranyi L (2002) Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes 51:1102–1109

    Article  CAS  PubMed  Google Scholar 

  • Lee YH, Giraud J, Davis RJ, White MF (2003) c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. J Biol Chem 278:2896–2902

    Article  CAS  PubMed  Google Scholar 

  • Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  • Meriin AB, Yaglom JA, Gabai VL, Zon L, Ganiatsas S, Mosser DD, Zon L, Sherman MY (1999) Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72. Mol Cell Biol 19:2547–2555

    CAS  PubMed Central  PubMed  Google Scholar 

  • Myers J, Bellin D (2000) Ramp exercise protocols for clinical and cardiopulmonary exercise testing. Sports Med 30:23–29

    Article  CAS  PubMed  Google Scholar 

  • O'Leary VB, Marchetti CM, Krishman RK, Stetzer BP, Gonzalez F, Kirwan JP (2006) Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat. J Appl Physiol 100:1584–1589

    Article  PubMed  Google Scholar 

  • Park HS, Lee JS, Huh SH, Seo JS, Choi EJ (2001) Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J 20:446–456

    Article  CAS  PubMed  Google Scholar 

  • Poole DC, Wilkerson DP, Jones AM (2008) Validity of criteria for establishing maximal O2 uptake during ramp exercise tests. Eur J Appl Physiol 102:403–410

    Article  CAS  PubMed  Google Scholar 

  • Richter EA, Mikines KJ, Galbo H, Kiens B (1989) Effect of exercise on insulin action in human skeletal muscle. J Appl Physiol 66:876–888

    CAS  PubMed  Google Scholar 

  • Ropelle ER, Pauli JR, Prada PO, de Souza CT, Picardi PK, Faria MC, Cintra DE, Fernandes MF, Flores MB, Velloso LA, Saad MJ, Carvalheira JB (2006) Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation. J Physiol 577:997–1007

    Article  CAS  PubMed  Google Scholar 

  • Sasai H, Sairenchi T, Iso H, Irie F, Otaka E, Tanaka K, Ota H, Muto T (2010) Relationship between obesity and incident diabetes in middle-aged and older Japanese adults: the Ibaraki Prefectural Health Study. Mayo Clin Proc 85:36–40

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Horowitz JF (2007) Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest 117:1690–1698

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shafrir E (1996) Development and consequences of insulin resistance: lessons from animals with hyperinsulinaemia. Diabetes Metab 22:122–131

    CAS  PubMed  Google Scholar 

  • Simar D, Jacques A, Caillaud C (2012) Heat shock proteins induction reduces stress kinases activation, potentially improving insulin signalling in monocytes from obese subjects. Cell Stress Chaperones 17:615–621

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sinha R, Fisch G, Teague BRN, Tamborlane WV, Banyas RNB, Allen KRN, Savoye MRD, Rieger VMD, Taksali SMPH, Barbetta GRD, Sherwin RSE, Caprio S (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346:802–810

    Article  CAS  PubMed  Google Scholar 

  • Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389:610–614

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization (2013) Global Health Observatory. Obesity. http://www.who.int/gho/ncd/risk_factors/obesity_text/en/index.html. Accessed 13 May 2013

  • Yi Z, Langlais P, De Filippis EA, Luo M, Flynn CR, Schroeder S, Weintraub ST, Mapes R, Mandarino LJ (2007) Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. Diabetes 56:1508–1516

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by CAPES (PNPD-2455/2011), FAPEMIG (CDS APQ01621-10), and CNPq (477154/2011-5) grants. The authors wish to acknowledge Dr. Valmor Alberto Augusto Tricoli of the University of São Paulo for teaching us the muscle biopsy technique, and Dr. David Lee Nelson for reviewing the manuscript.

Conflict of interest

The authors have no conflict of interests.

Author information

Authors and Affiliations

  1. Exercise Physiology Laboratory, Healthy and Biological Sciences Faculty, Federal University of Jequitinhonha and Mucuri Valleys, Rua da Glória 187, Diamantina, 39100-100, Minas Gerais, Brazil

    Mariana Aguiar de Matos, Vinícius de Oliveira Ottone, Tamiris Campos Duarte, Pâmela Fiche da Matta Sampaio, Karine Beatriz Costa, Cheyenne Alves Fonseca, Miguel Pontes Correa Neves, Flávio de Castro Magalhães, Etel Rocha-Vieira & Fabiano Trigueiro Amorim

  2. University of New Mexico, Albuquerque, NM, USA

    Suzanne Maria Schneider & Pope Moseley

  3. Endocrinology Laboratory, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Cândido Celso Coimbra

Authors
  1. Mariana Aguiar de Matos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vinícius de Oliveira Ottone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamiris Campos Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pâmela Fiche da Matta Sampaio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karine Beatriz Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheyenne Alves Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miguel Pontes Correa Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suzanne Maria Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pope Moseley
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cândido Celso Coimbra
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Flávio de Castro Magalhães
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Etel Rocha-Vieira
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fabiano Trigueiro Amorim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabiano Trigueiro Amorim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matos, M.A., Ottone, V.O., Duarte, T.C. et al. Exercise reduces cellular stress related to skeletal muscle insulin resistance. Cell Stress and Chaperones 19, 263–270 (2014). https://doi.org/10.1007/s12192-013-0453-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-013-0453-8

Keywords

Search

Navigation