Skip to main content

Advertisement

SpringerLink
Log in

Effects of exercise training on excitation–contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Although, several novel forms of intervention aiming at newly identified therapeutic targets are currently being developed for diabetes mellitus (DM), it is well established that physical exercise continues to be one of the most valuable forms of non-pharmacological therapy. The aim of the study was to investigate the effects of exercise training on excitation–contraction coupling and related gene expression in the Goto-Kakizaki (GK) type 2 diabetic rat heart and whether exercise is able to reverse diabetes-induced changes in excitation–contraction coupling and gene expression. Experiments were performed in GK and control rats aged 10–11 months following 2–3 months of treadmill exercise training. Shortening, [Ca2+]i and L-type Ca2+ current were measured in ventricular myocytes with video edge detection, fluorescence photometry and whole cell patch clamp techniques, respectively. Expression of mRNA was assessed in ventricular muscle with real-time RT-PCR. Amplitude of shortening, Ca2+ transients and L-type Ca2+ current were not significantly altered in ventricular myocytes from GK sedentary compared to control sedentary rats or by exercise training. Expression of mRNA encoding Tpm2, Gja4, Atp1b1, Cacna1g, Cacnb2, Hcn2, Kcna3 and Kcne1 were up-regulated and Gja1, Kcnj2 and Kcnk3 were down-regulated in hearts of sedentary GK rats compared to sedentary controls. Gja1, Cav3 and Kcnk3 were up-regulated and Hcn2 was down-regulated in hearts of exercise trained GK compared to sedentary GK controls. Ventricular myocyte shortening and Ca2+ transport were generally well preserved despite alterations in the profile of expression of mRNA encoding a variety of cardiac muscle proteins in the adult exercise trained GK diabetic rat heart.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Zimmet PZ, Alberti KG (2006) Introduction: globalization and the non-communicable disease epidemic. Obesity (Silver Spring) 14(1):1–3

    Article  Google Scholar 

  2. Malik M, Bakir A, Saab BA, King H (2005) Glucose intolerance and associated factors in the multi-ethnic population of the United Arab Emirates: results of a national survey. Diabetes Res Clin Pract 69(2):188–195

    Article  CAS  PubMed  Google Scholar 

  3. Julien J (1997) Cardiac complications in non-insulin-dependent diabetes mellitus. J Diabetes Complications 11:123–130

    Article  CAS  PubMed  Google Scholar 

  4. Chareonthaitawee P, Sorajja P, Rajagopalan N, Miller TD, Hodge DO, Frye RL, Gibbons RJ (2007) Prevalence and prognosis of left ventricular systolic dysfunction in asymptomatic diabetic patients without known coronary artery disease referred for stress single-photon emission computed tomography and assessment of left ventricular function. Am Heart J 154(3):567–574

    Article  PubMed  Google Scholar 

  5. Dounis V, Siegmund T, Hansen A, Jensen J, Schumm-Draeger PM, von Bibra H (2006) Global myocardial perfusion and diastolic function are impaired to a similar extent in patients with type 2 diabetes mellitus and in patients with coronary artery disease—evaluation by contrast echocardiography and pulsed tissue Doppler. Diabetologia 49(11):2729–2740

    Article  CAS  PubMed  Google Scholar 

  6. Loimaala A, Groundstroem K, Majahalme S, Nenonen A, Vuori I (2006) Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness. Eur J Echocardiogr 7(5):341–347

    Article  PubMed  Google Scholar 

  7. Annonu AK, Fattah AA, Mokhtar MS, Ghareeb S, Elhendy A (2001) Left ventricular systolic and diastolic functional abnormalities in asymptomatic patients with non-insulin-dependent diabetes mellitus. J Am Soc Echocardiogr 14(9):885–891

    Article  CAS  PubMed  Google Scholar 

  8. Zabalgoitia M, Ismaeil MF, Anderson L, Maklady FA (2001) Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus. Am J Cardiol 87(3):320–323

    Article  CAS  PubMed  Google Scholar 

  9. Di Bonito P, Cuomo S, Moio N, Sibilio G, Sabatini D, Quattrin S, Capaldo B (1996) Diastolic dysfunction in patients with non-insulin-dependent diabetes mellitus of short duration. Diabet Med 13(4):321–324

    Article  PubMed  Google Scholar 

  10. Hiramatsu K, Ohara N, Shigematsu S, Aizawa T, Ishihara F, Niwa A, Yamada T, Naka M, Momose A, Yoshizawa K (1992) Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control. Am J Cardiol 70(13):1185–1189

    Article  CAS  PubMed  Google Scholar 

  11. Yasuda I, Kawakami K, Shimada T, Tanigawa K, Murakami R, Izumi S, Morioka S, Kato Y, Moriyama K (1992) Systolic and diastolic left ventricular dysfunction in middle-aged asymptomatic non-insulin-dependent diabetics. J Cardiol 22(2–3):427–438

    CAS  PubMed  Google Scholar 

  12. Pedersen BK, Saltin B (2006) Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports 16 Suppl 1:3–63

    Article  CAS  PubMed  Google Scholar 

  13. Chipkin SR, Klugh SA, Chasan-Taber L (2001) Exercise and diabetes. Cardiol Clin 19(3):489–505

    Article  CAS  PubMed  Google Scholar 

  14. Howarth FC, Almugaddum FA, Qureshi MA, Ljubisavljevic M (2009) The effects of heavy long-term exercise on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin-induced diabetic rat. J Diabetes Complications 24(4):278–285

    Article  PubMed  Google Scholar 

  15. Howarth FC, Almugaddum FA, Qureshi MA, Ljubisavijevic M (2008) Effects of varying intensity exercise on shortening and intracellular calcium in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats. Mol Cell Biochem 317(1–2):161–167

    Article  CAS  PubMed  Google Scholar 

  16. Howarth FC, Qureshi MA, Hassan Z, Al Kury LT, Isaev D, Parekh K, Yammahi SR, Oz M, Adrian TE, Adeghate E (2011) Changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of Ca2+ signalling in young type 2 Zucker diabetic fatty rat heart. Exp Physiol 96(3):325–337

    Article  CAS  PubMed  Google Scholar 

  17. Salem KA, Adrian TE, Qureshi MA, Parekh KA, Oz M, Howarth FC (2012) Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats. Exp Physiol 97(12):1281–1291

    Article  CAS  PubMed  Google Scholar 

  18. Schrijvers BF, De Vriese AS, Van d V, Rasch R, Lameire NH, Flyvbjerg A (2004) Long-term renal changes in the Goto-Kakizaki rat, a model of lean type 2 diabetes. Nephrol Dial Transplant 19(5):1092–1097

    Article  PubMed  Google Scholar 

  19. Grijalva J, Hicks S, Zhao X, Medikayala S, Kaminski PM, Wolin MS, Edwards JG (2008) Exercise training enhanced myocardial endothelial nitric oxide synthase (eNOS) function in diabetic Goto-Kakizaki (GK) rats. Cardiovasc Diabetol 19(7):34. doi:10.1186/1475-2840-7-34

    Article  Google Scholar 

  20. Howarth FC, Jacobson M, Shafiullah M, Adeghate E (2008) Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat. Exp Physiol 93(3):362–369

    Article  PubMed  Google Scholar 

  21. Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S, Gronholm M, Wallgren-Pettersson C (2012) Abnormal actin binding of aberrant beta-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy. Biochem J 442(1):231–239

    Article  CAS  PubMed  Google Scholar 

  22. Delmar M, Makita N (2012) Cardiac connexins, mutations and arrhythmias. Curr Opin Cardiol 27(3):236–241

    Article  PubMed  Google Scholar 

  23. Meens MJ, Pfenniger A, Kwak BR (2012) Risky communication in atherosclerosis and thrombus formation. Swiss Med Wkly 142:w13553. doi:10.4414/smw.2012.13553.:w13553

    PubMed  Google Scholar 

  24. Barwe SP, Jordan MC, Skay A, Inge L, Rajasekaran SA, Wolle D, Johnson CL, Neco P, Fang K, Rozengurt N, Goldhaber JI, Roos KP, Rajasekaran AK (2009) Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na, K-ATPase beta1-subunit. J Mol Cell Cardiol 47(4):552–560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Mangoni ME, Traboulsie A, Leoni AL, Couette B, Marger L, Le Quang K, Kupfer E, Cohen-Solal A, Vilar J, Shin HS, Escande D, Charpentier F, Nargeot J, Lory P (2006) Bradycardia and slowing of the atrioventricular conduction in mice lacking CaV3.1/alpha1G T-type calcium channels. Circ Res 98(11):1422–1430

    Article  CAS  PubMed  Google Scholar 

  26. Meissner M, Weissgerber P, Londono JE, Prenen J, Link S, Ruppenthal S, Molkentin JD, Lipp P, Nilius B, Freichel M, Flockerzi V (2011) Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the cacnb2 gene. J Biol Chem 286(18):15875–15882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Herrmann S, Layh B, Ludwig A (2011) Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart. J Mol Cell Cardiol 51(6):997–1006

    Article  CAS  PubMed  Google Scholar 

  28. Xia S, Wang Y, Zhang Y, Deng SB, Du JL, Wang XC, She Q (2010) Dynamic changes in HCN2, HCN4, KCNE1, and KCNE2 expression in ventricular cells from acute myocardial infarction rat hearts. Biochem Biophys Res Commun 395(3):330–335

    Article  CAS  PubMed  Google Scholar 

  29. Manabe I, Tsuboi M, Ahmmed GU, Sasaki N, Ohtahara A, Yamamoto Y, Hiroe K, Yoshida A, Hisatome I, Shigemasa C (1998) Expression of Shaker-type voltage-gated potassium channel genes in the guinea-pig. Res Commun Mol Pathol Pharmacol 99(1):33–40

    CAS  PubMed  Google Scholar 

  30. Brahmajothi MV, Morales MJ, Rasmusson RL, Campbell DL, Strauss HC (1997) Heterogeneity in K+ channel transcript expression detected in isolated ferret cardiac myocytes. Pacing Clin Electrophysiol 20(2 Pt 2):388–396

    Article  CAS  PubMed  Google Scholar 

  31. Liu Z, Du L, Li M (2012) Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function. Curr Med Chem 19(9):1405–1420

    Article  CAS  PubMed  Google Scholar 

  32. Guo J, Wang T, Yang T, Xu J, Li W, Fridman MD, Fisher JT, Zhang S (2011) Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+ -induced hERG endocytic degradation. J Biol Chem 286(40):34664–34674

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Grunnet M (2010) Repolarization of the cardiac action potential. Does an increase in repolarization capacity constitute a new anti-arrhythmic principle? Acta Physiol (Oxf) 198 Suppl 676:1–48

    Article  CAS  Google Scholar 

  34. Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R (2002) Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 110(3):381–388

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Gierten J, Ficker E, Bloehs R, Schweizer PA, Zitron E, Scholz E, Karle C, Katus HA, Thomas D (2010) The human cardiac K2P3.1 (TASK-1) potassium leak channel is a molecular target for the class III antiarrhythmic drug amiodarone. Naunyn Schmiedebergs Arch Pharmacol 381(3):261–270

    Article  CAS  PubMed  Google Scholar 

  36. Besana A, Barbuti A, Tateyama MA, Symes AJ, Robinson RB, Feinmark SJ (2004) Activation of protein kinase C epsilon inhibits the two-pore domain K+ channel, TASK-1, inducing repolarization abnormalities in cardiac ventricular myocytes. J Biol Chem 279(32):33154–33160

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from UAE University and Emirates Foundation. Research in our laboratory is also supported by LABCO a partner of Sigma-Aldrich.

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine & Health Sciences, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE

    M. A. Qureshi, V. Sydorenko, K. Parekh, P. Jayaprakash, T. E. Adrian & F. C. Howarth

  2. Department of Pharmacology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE

    K. A. Salem & M. Oz

  3. School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Lancashire, UK

    T. Iqbal & J. Singh

Authors
  1. K. A. Salem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. Qureshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Sydorenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Parekh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Jayaprakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Oz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T. E. Adrian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. C. Howarth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. C. Howarth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salem, K.A., Qureshi, M.A., Sydorenko, V. et al. Effects of exercise training on excitation–contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats. Mol Cell Biochem 380, 83–96 (2013). https://doi.org/10.1007/s11010-013-1662-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1662-2

Keywords

Search

Navigation