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Heart Failure Reviews

, Volume 20, Issue 5, pp 589–600 | Cite as

The role of CaMKII in diabetic heart dysfunction

  • Lorna Daniels
  • James R. Bell
  • Lea M. D. Delbridge
  • Fiona J. McDonald
  • Regis R. Lamberts
  • Jeffrey R. EricksonEmail author
Article

Abstract

Diabetes mellitus (DM) is an increasing epidemic that places a significant burden on health services worldwide. The incidence of heart failure (HF) is significantly higher in diabetic patients compared to non-diabetic patients. One underlying mechanism proposed for the link between DM and HF is activation of calmodulin-dependent protein kinase (CaMKIIδ). CaMKIIδ mediates ion channel function and Ca2+ handling during excitation–contraction and excitation-transcription coupling in the myocardium. CaMKIIδ activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis. Pharmacological inhibition and knockout models of CaMKIIδ have shown some promise of a potential therapeutic benefit of CaMKIIδ inhibition, with protection against cardiac hypertrophy and apoptosis reported. This review will highlight the pathological role of CaMKIIδ in diabetes and discuss CaMKIIδ as a therapeutic target in DM, and also the effects of exercise on CaMKIIδ.

Keywords

CaMKII Diabetes mellitus Diabetic heart dysfunction Heart failure Exercise 

Notes

Acknowledgments

This publication was written with support from the Marsden Fund of the Royal Society of New Zealand (13-UOO-193) for J.R.E. and a University of Otago Department of Physiology scholarship for L.D.

Compliance with ethical standards

Conflicts of interest

There are no conflicts of interest to disclose for any of the authors.

References

  1. 1.
    Whiting DR, Guariguata L, Weil C, Shaw J (2011) IDF diabetes atlas: global estimate of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94:311–321PubMedGoogle Scholar
  2. 2.
    Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149PubMedGoogle Scholar
  3. 3.
    Kannel WB, McGee DL (1979) Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes Care 2:120–126PubMedGoogle Scholar
  4. 4.
    Marwick TH (2006) Diabetic heart disease. Heart 92:296–300PubMedCentralPubMedGoogle Scholar
  5. 5.
    Hayat SA, Patel B, Khattar RS, Malik RA (2004) Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci 107:539–557PubMedGoogle Scholar
  6. 6.
    Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 30:595–602PubMedGoogle Scholar
  7. 7.
    Malmberg K, Ryden L (1987) Myocardial infarction in patients with diabetes mellitus. Eur Heart J 9:259–264Google Scholar
  8. 8.
    Adeghate E (2004) Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. Mol Cell Biochem 18:1–5Google Scholar
  9. 9.
    Simone G, Devereux RB, Howard BV (2010) Diabetes and incident heart failure in hypertensive and normotensive participants of the strong heart study. J Hypertens 28:353–360PubMedCentralPubMedGoogle Scholar
  10. 10.
    Asmal AC, Leary WP, Thandroyen F (1980) Diabetic heart disease. S Afr Med J 57:788–790PubMedGoogle Scholar
  11. 11.
    Rawal S, Manning P, Katare R (2014) Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease. Cardiovasc Diabetol 13:1–24Google Scholar
  12. 12.
    Bugger H, Abel ED (2014) Molecular mechanisms of diabetic cardiomyopathy. Diabetologia 57:660–671PubMedCentralPubMedGoogle Scholar
  13. 13.
    Hasenfuss G (1997) Calcium handling proteins in the failing human heart. Basic Res Cardiol 92:87–93PubMedGoogle Scholar
  14. 14.
    Hasenfuss G (1998) Alterations of calcium-regulatory proteins in heart failure. Cardiovasc Res 37:279–289PubMedGoogle Scholar
  15. 15.
    Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. JMCC 34:951–969Google Scholar
  16. 16.
    Bers DM (2006) Altered cardiac myocyte Ca2+ regulation in heart failure. Physiology 21:380–387PubMedGoogle Scholar
  17. 17.
    Ather S, Rrespress JL, Li Na L, Wehrens XHT (2013) Alterations in ryanodine receptors and related proteins in heart failure. Biochim Biophys Acta 1832:2425–2431PubMedGoogle Scholar
  18. 18.
    Luo M, Anderson ME (2013) Mechanisms of altered Ca2+ handling in heart failure. Circ Res 113:690–708PubMedCentralPubMedGoogle Scholar
  19. 19.
    Fabiato A, Fabiato F (1979) Calcium and cardiac excitation-contraction coupling. Ann Rev Physiol 41:473–484Google Scholar
  20. 20.
    Bers DM (2008) Excitation-contraction coupling and cardiac contractile force. In: Excitation contraction coupling and cardiac contractile force, 2nd edn. Springer, Netherlands, pp 203–244Google Scholar
  21. 21.
    Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198–205PubMedGoogle Scholar
  22. 22.
    Fabiato A (1983) Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:1–14Google Scholar
  23. 23.
    Stern MD, Capogrossi MC, Lakatta EG (1988) Spontaneous calcium release from the sarcoplasmic reticulum in myocardial cells: mechanisms and consequences. Cell Calcium 9:247–256PubMedGoogle Scholar
  24. 24.
    Lukyanenko V, Gyorke I, Gyorke S (1996) Regulation of calcium release by calcium inside the sarcoplasmic reticulum in ventricular myocytes. Eur J Physiol 432:1047–1054Google Scholar
  25. 25.
    Solaro RJ, Rarick HM (1998) Troponin and tropomyosin proteins that switch on and tune in the activity of cardiac myofilaments. Circ Res 83:471–480PubMedGoogle Scholar
  26. 26.
    Bers DM (2000) Calcium fluxes involved in control of cardiac myocyte contraction. Circ Res 87:275–281PubMedGoogle Scholar
  27. 27.
    Zhang X, Chen C (2012) A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy. Endocrine 41:398–409PubMedGoogle Scholar
  28. 28.
    Lopaschuk GD, Tahiliani AG, Vadlamudi RV, Katz S, McNeill JH (1983) Cardiac sarcoplasmic reticulum function in insulin-or carnitine-treated diabetic rats. Am J Physiol Heart Circ Physiol 245:969–976Google Scholar
  29. 29.
    Flarsheim CE, Grupp IL, Matlib MA (1996) Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart. Am J Physiol Heart Circ Physiol 271:192–202Google Scholar
  30. 30.
    Ye G, Metreveli NS, Ren J, Epstein PN (2003) Metallothionein prevents diabetes-induced deficits in cardiomyocytes by inhibiting reactive oxygen species production. Diabetes 52:777–783PubMedGoogle Scholar
  31. 31.
    Ye G, Metreveli NS, Donthi RV, Xia S, Xu M, Carlson EC, Epstein PN (2004) Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. Diabetes 53:1336–1343PubMedGoogle Scholar
  32. 32.
    Kralik PM, Ye G, Metreveli NS, Shem X, Epstein PN (2005) Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes. Cardiovasc Toxicol 5:285–292PubMedGoogle Scholar
  33. 33.
    Bugger H, Abel ED (2009) Rodent models of diabetic cardiomyopathy. Dis Model Mech 2:454–466PubMedGoogle Scholar
  34. 34.
    Belke DD, Swanson EA, Dillmann WH (2004) Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes 53:3201–3208PubMedGoogle Scholar
  35. 35.
    Pereira L, Matthes J, Schuster I, Valdiva HH, Herzig S, Richard S, Gomez AM (2006) Mechanisms of [Ca2+] transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes 55:608–615PubMedGoogle Scholar
  36. 36.
    Chelu MG, Sarma S, Sood S, Wang S, van Oort RJ, Skapura DG et al (2009) Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest 119:1940–1951PubMedCentralPubMedGoogle Scholar
  37. 37.
    Fischer TH, Herting J, Tirilomis T, Renner A, Neef S, Toischer K et al (2013) CaMKII and PKA differentially regulate SR Ca2=- leak in human cardiac pathology. Circ 128:970–981Google Scholar
  38. 38.
    Fischer TH, Eiringhaus J, Dybkova N, Forster A, Herting J, Kleinwachter A et al (2014) Ca(2+)/calmodulin-dependent protein kinase II equally induces sarcoplasmic reticulum Ca(2+) leak in human ischaemic dilated cardiomyopathy. Eur J Heart Fail 16:1292–1300PubMedGoogle Scholar
  39. 39.
    Neef S, Dybkova N, Sossalla S, Ort KR, Fluschnik N, Neumann K et al (2010) CaMKII dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ Res 106:1134–1144PubMedGoogle Scholar
  40. 40.
    Maier LS, Zhang T, Chen L, DeSantiago J, Brown JH, Bers DM (2003) Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res 92:904–911PubMedGoogle Scholar
  41. 41.
    Maier LS, Bers DM (2002) Calcium, calmodulin and calcium-calmodulin kinase II: heartbeat to heartbeat and beyond. J Moll Cell Cardiol 34:919–939Google Scholar
  42. 42.
    Zhang T, Brown JH (2004) Role of Ca2+/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure. Cardiovas Res 63:476–486Google Scholar
  43. 43.
    Braun AP, Schulman H (2005) The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. Annu Rev Physiol 57:417–445Google Scholar
  44. 44.
    Lin CR, Kapiloff MS, Durgerian S, Tatemoto K, Russo AF, Hanson P et al (1987) Molecular cloning of a brain-specific calcium-calmodulin-dependent protein kinase. Proc Natl Acad Sci USA 84:5962–5966PubMedCentralPubMedGoogle Scholar
  45. 45.
    Kelly PT, Weinburger RP, Waxham MN (1988) Active site-directed inhibition of Ca2+/calmodulin-dependent protein kinase type II by a bifunctional calmodulin-binding peptide. Proc Natl Acad Sci USA 85:4991–4995PubMedCentralPubMedGoogle Scholar
  46. 46.
    Colbran RJ, Fong YL, Schworer CM, Soderling TR (1988) Regulatory interactions of the calmodulin-binding, inhibitory and autophosphorylation domains of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem 263:18145–18151PubMedGoogle Scholar
  47. 47.
    Smith MK, Colbran RJ, Bricky DA, Soderling TR (1992) Functional determinants in the autoinhibitory domain of calcium/calmodulin-dependent protein kinase II. Role of His282 and multiple basic residues. J Biol Chem 267:1761–1768PubMedGoogle Scholar
  48. 48.
    Lou LL, Lloyd SJ, Schulman H (1986) Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase by autophosphorylation: ATP modulates production of an autonomous enzyme. Proc Natl Acad Sci USA 83:9497–9501PubMedCentralPubMedGoogle Scholar
  49. 49.
    Meyer T, Hanson PI, Stryer L, Schulman H (1992) Calmodulin trapping by calcium-calmodulin-dependent protein kinase. Science 256:1199–1201PubMedGoogle Scholar
  50. 50.
    De Koninck P, Schulman H (1998) Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science 279:227–230PubMedGoogle Scholar
  51. 51.
    Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV et al (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133:462–474PubMedCentralPubMedGoogle Scholar
  52. 52.
    Erickson JR, He JB, Grumbach IM, Anderson ME (2011) CaMKII in the cardiovascular system: sensing redox states. Physiol Rev 91:889–915PubMedCentralPubMedGoogle Scholar
  53. 53.
    Zhang DM, Chai Y, Erickson JR, Brown JH, Bers DM, Lin YF (2014) Intracellular signaling mechanism responsible for modulation of sarcolemmal ATP-sensitive potassium channels by nitric oxide in ventricular cardiomyocytes. J Physiol 592:971–990PubMedCentralPubMedGoogle Scholar
  54. 54.
    Coultrap SJ, Bayer KU (2014) Nitric oxide induces Ca2+ independent activity of the Ca2+/calmodulin- dependent protein kinase II (CaMKII). J Biol Chem 28:19458–19465Google Scholar
  55. 55.
    Hudman A, Schulman H (2002) Neuronal Ca2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Ann Rev Biochem 71:473–510Google Scholar
  56. 56.
    Erickson JR (2014) Mechanisms of CaMKII activation in the heart. Frontiers in Pharm Res 59:1–5Google Scholar
  57. 57.
    Torres CR, Hart GW (1984) Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J Biol Chem 259:3308–3317PubMedGoogle Scholar
  58. 58.
    Zachara NE, Hart GW (2004) O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress. Biochem Biophys Acta 1673:13–28PubMedGoogle Scholar
  59. 59.
    Zachara NE, Hart GW (2006) Cell signaling, the essential role of O-GlcNAc! Biochem Biophys Acta 1761:599–617PubMedGoogle Scholar
  60. 60.
    Hart GW (1997) Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. Annu Rev Biochem 66:315–335PubMedGoogle Scholar
  61. 61.
    Wells L, Whalen SA, Hart GW (2003) A regulatory post-translational modification. Biochem Biophys Res Commun 302:435–441PubMedGoogle Scholar
  62. 62.
    Comer FI, Hart GW (1999) O-GlcNAc and the control of gene expression. Biochem Biophys Acta 1473:161–171PubMedGoogle Scholar
  63. 63.
    McLarty JL, Marsh SA, Chatham JC (2013) Post-translational protein modification by O-linked N-acetyl-glucosamine: its role in mediating the adverse effects of diabetes on the heart. Life Sci 92:621–627PubMedCentralPubMedGoogle Scholar
  64. 64.
    Chatham JC, Marchase RB (2010) The role of protein O-linked B-N-acetylglucosamine in mediating cardiac stress response. Biochem Biophys Acta 1800:57–66PubMedCentralPubMedGoogle Scholar
  65. 65.
    Medford HM, Chatham JC, Marsh SA (2012) Chronic ingestion of a western diet increases O-linked-B-N-acetylglucosamine (O-GlcNAc) protein modification in the rat heart. Life Sci 90:23–24Google Scholar
  66. 66.
    Taylor RP, Parker GJ, Hazel MW, Soesanto Y, Fuller W, Yazzie MJ et al (2008) Glucose deprivation stimulates O-GlcNAC modification of proteins through upregulation of O-linked N-acetylglucosaminyltransferase. J Biol Chem 283:6050–6057PubMedGoogle Scholar
  67. 67.
    Zou L, Zhu-Maldin Z, Marchase RB, Paterson AJ, Liu J, Yang Q, Chatham JC (2012) Glucose deprivation-induced increase in protein O-GlcNAcylation in cardiomyocytes is calcium dependent. J Biol Chem 287:34419–34431PubMedCentralPubMedGoogle Scholar
  68. 68.
    Hu Y, Belke D, Suarez J, Swanson E, Clark R, Hoshijima M et al (2005) Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart. Circ Res 96:1006–1013PubMedGoogle Scholar
  69. 69.
    Yokoe S, Ashai M, Takeda T, Otsu K, Taniguchi N, Miyoshi E et al (2010) Inhibition of phospholamban phosphorylation by O-GlcNAcylation: implications for diabetic cardiomyopathy. Glycobio 20:1217–1226Google Scholar
  70. 70.
    Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K et al (2013) Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycolysation. Nature 502:372–376PubMedCentralPubMedGoogle Scholar
  71. 71.
    Liu J, Marchase RB, Chatham JC (2007) Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increase protein O-GlcNAc levels. JMCC 42:177–185Google Scholar
  72. 72.
    Zachara NE, O’Donnell N, Cheng WD, Mercer JJ, Marth JD, Hart GW (2004) Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress: a survival response in mammalian cells. J Biol Chem 279:30133–30142PubMedGoogle Scholar
  73. 73.
    Zou L, Yang S, Hu S, Chaudry IH, Marchase RB, Chatham JC (2007) The protective effects of PUGNAc on cardiac function after trauma-hemorrhage are mediated via increase protein O-GlcNAc levels. Shock 27:402–408PubMedGoogle Scholar
  74. 74.
    Zou L, Yang S, Champattanachai V, Hu S, ChauDRY IH, Marchase RB et al (2009) Glucosamine improves cardiac function following trauma-hemorrhage by increase protein O-GlcNAcylation and attenuation of NF-(kappa) b signaling. Am J Physiol Heart Circ Physiol 296:515–523Google Scholar
  75. 75.
    Anderson ME, Brown JH, Bers DM (2011) CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol 51:468–473PubMedCentralPubMedGoogle Scholar
  76. 76.
    Swaminathan PD, Purohit A, Hund TJ, Anderson ME (2012) Calmodulin-dependent protein kinase II: linking heart failure and arrhythmias. Circ Res 110:1661–1677PubMedCentralPubMedGoogle Scholar
  77. 77.
    Couchonnal LF, Anderson ME (2008) The role of calmodulin kinase II in myocardial physiology and disease. Physiology 23:151–159PubMedGoogle Scholar
  78. 78.
    Witcher DR, Kovacs RJ, Schulman H, Cefali DC, Jones LR (1991) Unique phosphorylation site on the cardiac ryanodine receptor regulates calcium channel activity. J Biol Chem 266:11144–11152PubMedGoogle Scholar
  79. 79.
    Wehrens XH, Lehnart SE, Reiken SR, Marks AR (2004) Ca2+/calmodulin dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ Res 94:61–70Google Scholar
  80. 80.
    Simmerman HK, Collins JH, Theibert JL, Wegener AD, Jones LR (1986) Sequence analysis of phospholamban. Identification of phosphorylation sites and two major structural domains. J Biol Chem 261:13333–13341PubMedGoogle Scholar
  81. 81.
    Brittsan AG, Kranias EG (2000) Phospholamban and cardiac contractile function. J Mol Cell Card 32:2131–2139Google Scholar
  82. 82.
    Hook SS, Means AR (2001) Ca2+/CaM-dependent kinases: from activation to function. Annu Rev Pharmacol Toxicol 41:471–505PubMedGoogle Scholar
  83. 83.
    Kirchhefer U, Schmitz W, Scholz H, Neumann J (1999) Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts. Cardiovas Res 42:254–261Google Scholar
  84. 84.
    Hoch B, Meyer R, Hetzer R, Krause EG, Karczewski P (1999) Identification and expression of δ isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium. Circ Res 84:713–721PubMedGoogle Scholar
  85. 85.
    Sossalla S, Fluschnik N, Schotola H, Ort KR, Neef S, Schulte T et al (2010) Inhibition of elevated Ca2+/calmdoulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 107:1150–1161PubMedGoogle Scholar
  86. 86.
    Zhang T, Maier LS, Dalton ND, Miyamoto S, Ross J, Donald M et al (2003) The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res 92:912–919PubMedGoogle Scholar
  87. 87.
    Reuter H, Gronke S, Adam C, Ribati M, Brabender J, Zobel C et al (2008) Sarcoplasmic Ca2+ release is prolonged in nonfailing myocardium of diabetic patients. Mol Cell Biochem 308:141–149PubMedGoogle Scholar
  88. 88.
    Lamberts RR, Lingam SJ, Wang H, Bollen IAE, Hughes G, Galvin IF et al (2014) Impaired relaxation despite upregulated calcium-handling pro in atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovasr diabetol 13:72Google Scholar
  89. 89.
    Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9PubMedGoogle Scholar
  90. 90.
    Jay D, Hitomi H, Griendling KK (2006) Oxidative stress and diabetic cardiovascular complications. Free Rad Bio Med 40:183–192Google Scholar
  91. 91.
    Luo M, Guan X, Luczak ED, Lang D, Kutschke W, Gao Z et al (2013) Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest 123:1262–1274PubMedCentralPubMedGoogle Scholar
  92. 92.
    Purohit A, Rokita AG, Guan X, Chen B, Koval OM, Voigt N et al (2013) Oxidized CaMKII triggers atrial fibrillation. Circulation 128:1748–1757PubMedGoogle Scholar
  93. 93.
    Song Y, Shryock JC, Belardinelli L (2008) An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes. Am J Physiol Heart Circ Physiol 294:2031–2039Google Scholar
  94. 94.
    Swaminathan PD, Purohit A, Soni S, Voigt N, Singh MV, Glukhov AV et al (2011) Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 121:3277–3288PubMedCentralPubMedGoogle Scholar
  95. 95.
    Voigt N, Li N, Wang Q, Wang W, Trafford AW, Abu-Taha I et al (2012) Enhanced sarcoplasmic reticulum Ca2+ leak and increased Na+–Ca2+ exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circ 125:2059–2070Google Scholar
  96. 96.
    Weiss JN, Garfinkel A, Karaguezian HS, Chen P, Qu Z (2010) Early afterdepolarizations and cardiac arrhythmias. Heart rhythm 7:1891–1899PubMedCentralPubMedGoogle Scholar
  97. 97.
    Westenbrink BD, Edwards AG, McCulloch AD, Brown JH (2013) The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias. Expert Opin Ther Targets 17:889–903PubMedGoogle Scholar
  98. 98.
    Luczak ED, Anderson ME (2014) CaMKII oxidative activation and the pathogenesis of cardiac disease. JMCC 73:112–116Google Scholar
  99. 99.
    Roden DM, Lazzara R, Rosen M, Schwartz PJ, Towhin J, Vincent GM (1996) Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps and future directions. The SADS foundation task force on LQTS. Circ 94:1996–2012Google Scholar
  100. 100.
    Anderson ME, Braun AP, Wu Y, Lu T, Wu Y, Schulman H, Sung RJ (1998) KN-93 an inhibitor of multifunctional Ca++/calmodulin-depenent protein kinase, decreases early afterdepolarization in rabbit heart. J Pharm Exp Tech 287:996–1006Google Scholar
  101. 101.
    Venetucci LA, Trafford AW, O’Neill SC, Eisner DA (2008) The sarcoplasmic reticulum and arrhythmogenic calcium release. Cardiovas Res 77:285–292Google Scholar
  102. 102.
    Wright SC, Schellenberger U, Ji L, Wang H, Larrick JW (1997) Calmodulin-dependent protein kinase II mediates signal transduction in apoptosis. FASEBJ 11:843–849Google Scholar
  103. 103.
    Ishitani T, Kishida S, Hyodo-Miura J, Ueno N, Yasuda J, Waterman M et al (2003) The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca2+ pathway to antagonize Wnt/B-catening signaling. Mol Cell Bio 23:131–139Google Scholar
  104. 104.
    Takeda K, Matsuzawa A, Nishitoh H, Tobiume K, Kishida S, Ninomiya-Tsjui J et al (2004) Involvement of ASK1 in Ca2+-induced p38 MAP kinase activation. EMBO Rep 5:161–166PubMedCentralPubMedGoogle Scholar
  105. 105.
    Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T et al (1994) JNKI: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76:1025–1037PubMedGoogle Scholar
  106. 106.
    Dhanasekaran DN, Reddy EP (2008) JNK signaling in apoptosis. Oncogen 27:6245–6251Google Scholar
  107. 107.
    Zhu W, Woo AY, Yang D, Cheng H, Crow MT, Xiao R (2007) Activation of CaMKIIdeltaC is a common intermediate of diverse death stimuli-induced heart muscle cell apoptosis. J Biol Chem 282:10833–10839PubMedGoogle Scholar
  108. 108.
    Chen X, Zhang X, Kubo H, Harris DM, Mills GD, Moyer J et al (2005) Ca2+ influx induced sarcoplasmic reticulum Ca2+ overload causes mitochondrial-dependent apoptosis in ventricular myocytes. Circ Res 97:1009–1017PubMedGoogle Scholar
  109. 109.
    Joiner MA, Koval OM, Jingdong Li, He JB, Allamargot C, Gao Z et al (2012) CaMKII determines mitochondrial stress responses in heart. Nature 491:269–273PubMedCentralPubMedGoogle Scholar
  110. 110.
    Maisch B, Alter P, Pankuweit S (2011) Diabetic cardiomyopathy-fact or fiction? Herz 36:102–115PubMedGoogle Scholar
  111. 111.
    Cai L, Kang YJ (2001) Oxidative stress and cardiomyopathy: a brief review. Cardiovasc Toxicol 1:181–193PubMedGoogle Scholar
  112. 112.
    Ren J, Gintant GA, Miller RE, Davidoff AJ (1994) High extracellular glucose impairs cardiac E-C coupling in a glycolysation-dependent manner. Am J Physiol 273:2876–2883Google Scholar
  113. 113.
    Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M et al (2003) Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J Biol Chem 278:44230–44237PubMedGoogle Scholar
  114. 114.
    Cai L, Li Wei, Wang G, Guo L, Jiang Y, Kang YJ (2002) Hyperglycemia-induced apoptosis in mouse myocardium- mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetes 51:1938–1948PubMedGoogle Scholar
  115. 115.
    Backlund T, Palojoki E, Saraste A, Eriksson A, Finckenberg P, Kyto V et al (2004) Sustained cardiomyocytes apoptosis and left ventricular remodeling after myocardial infarction in experimental diabetes. Diabetologia 47:325–330PubMedGoogle Scholar
  116. 116.
    Zhang R, Kooh MSC, Wu Y, Yang Y, Grueter CE, Ni G et al (2005) Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 11:409–417PubMedGoogle Scholar
  117. 117.
    Backs J, Backs T, Neef S, Kreusser MM, Lehmann LH, Patrick DM et al (2009) The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci USA 106:2342–2347PubMedCentralPubMedGoogle Scholar
  118. 118.
    Ling H, Zhang T, Pereira L, Means CK, Cheng H, Gu Y et al (2009) Requirement for Ca2+/calmodulin-dependent kinase II in the transition from the pressure overload-induced cardiac hypertrophy to heart failure in mice. J Clin Invest 119:1230–1240PubMedCentralPubMedGoogle Scholar
  119. 119.
    Cheng J, Xu L, Lai D, Guilbert A, Lim HJ, Keskanokwong T et al (2012) CaMKII inhibition in heart failure, beneficial, harmful or both. Am J Physiol 302:1453–1465Google Scholar
  120. 120.
    Maier LS, Bers DM (2007) Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart. Cardiovas Res 73:631–640Google Scholar
  121. 121.
    Sumi M, Kiuchi K, Ishikawa T, Ishii A, Hagiwara M, Nagatsu T, Hidika H (1991) The newly synthesized selective Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12H cells. Biochem Biophys Res Commun 181:968–975PubMedGoogle Scholar
  122. 122.
    Ishida A, Kameshita I, Okuno S, Kitani T, Fujisawa H (1995) A novel specific and potent inhibitor of calmodulin-dependent protein kinase II. Biochem Biophys Res Commun 212:806–812PubMedGoogle Scholar
  123. 123.
    Sag CM, Wadsack DP, Khabbazzadeh S, Abesser M, Grefe C, Neumann K et al (2009) Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure. Circ Heart Fail 2:664–675PubMedCentralPubMedGoogle Scholar
  124. 124.
    Pellicena P, Schulamn H (2014) CaMKII inhibitors: from research tools to therapeutic agents. Front Pharma 5:1–10Google Scholar
  125. 125.
    Stolen TO, Hoydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E et al (2009) Interval training normalizes cardiomyocytes function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res 105:527–536PubMedGoogle Scholar
  126. 126.
    Chudyk A, Petrella RJ (2011) Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta analysis. Diabetes Care 34:1228–1237PubMedCentralPubMedGoogle Scholar
  127. 127.
    Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ (2001) Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta analysis of controlled trials. JAMA 286:1218–1227PubMedGoogle Scholar
  128. 128.
    Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tidesley HD, Frohlich JJ (2003) Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care 26:2977–2982PubMedGoogle Scholar
  129. 129.
    Bordenave S, Brandou F, Manetta J, Fedou C, Mercier J, Brun JF (2007) Effects of acute exercise on insulin sensitivity, glucose effectiveness and disposition index in type 2 diabetic patients. Diabetes Metab 34(250):257Google Scholar
  130. 130.
    Brassard P, Legault S, Garneau C, Bogaty P, Dumesnil JG, Poirier P (2007) Normalization of diastolic dysfunction in type 2 diabetics after exercise training. Med Sci Sports Exerc 39:1896–1901PubMedGoogle Scholar
  131. 131.
    Lamberts S, Van Laethem C, Van Acker K, Calders P (2008) Influence of combined exercise training on indices of obesity, diabetes and cardiovascular risk in type 2 diabetes patients. Clin Rehabil 22(483):492Google Scholar
  132. 132.
    Malfatto G, Facchini M, Bragato R, Branzi G, Sala L, Leonetti G (1996) Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction. Eur Heart J 17:532–538PubMedGoogle Scholar
  133. 133.
    Oldrige NB, Guyatt GG, Fischer ME, Rimm AA (1988) Cardiac rehabilitation after myocardial infarction: combined experience of randomized clinical trials. J Am Med Assoc 260:945–950Google Scholar
  134. 134.
    Philip A, Ades MD (2001) Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med 345:892–902Google Scholar
  135. 135.
    Taylor RS, Brown A, Ebrahim S, Joliffe J, Noorani H, Rees K et al (2003) Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med 116:682–692Google Scholar
  136. 136.
    Banzer JA, Maguire TE, Kennedy CM, O’Malley CJ, Balady GJ (2004) Results of cardiac rehabilitation in patients with diabetes mellitus. Am J Cardiol 93:81–84PubMedGoogle Scholar
  137. 137.
    Boukhris M, Tomasello D, Khanfir R, Elhadj Z, Terra AW, Marza F et al (2015) Impact of cardiac rehabilitation on ventricular repolarization indexes and ventricular arrhythmias in patients affected by coronary artery disease and type 2 diabetes. Heart Lung 44:199–204PubMedGoogle Scholar
  138. 138.
    Horden MD, Dunstan DW, Prins JB, Baker MK, Fiatarone Singh MA, Coombes JS (2012) Exercise prescription for patients with type 2 diabetes and pre-diabetes: a position statement from exercise and sport science Australia. J Sci Med Spor 15:25–31Google Scholar
  139. 139.
    Boule NG, Kenny GP, Haddad E, Wells GA, Sigal RJ (2003) Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia 46:1071–1081PubMedGoogle Scholar
  140. 140.
    Gibala MJ, Little JP, van Essen M, Wilkin GP, Burgomaster KA, Safdar A et al (2006) Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance. J Physiol 575:901–911PubMedCentralPubMedGoogle Scholar
  141. 141.
    Hood MS, Little JP, Tarnopolsky MA, Myslik F, Gibala MJ (2011) Low-volume interval training improves muscle oxidative capacity in sedentary adults. Med Sci Sports Exerc 43:1849–1856PubMedGoogle Scholar
  142. 142.
    Little JP, Safdar A, Wilkin GO, Tarnopolsky MA, Gibala MJ (2010) A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. J Physiol 588:1011–1022PubMedCentralPubMedGoogle Scholar
  143. 143.
    Bloomgarden ZT (1999) American Diabetes Association annual meeting—diabetes and obesity. Diabetes Care 23:118–124Google Scholar
  144. 144.
    Linke SE, Gallo LC, Norman GJ (2011) Attrition and adherence rates of sustained vs. intermittent exercise interventions. Ann Behav Med 42:197–209PubMedCentralPubMedGoogle Scholar
  145. 145.
    Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JF, Dela F (2004) Strength training increases insulin-mediated uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes 53:294–305PubMedGoogle Scholar
  146. 146.
    Yang Z, Scott CA, Mao C, Tang J, Farmer AJ (2013) Resistance exercise versus aerobic exercise for type 2 diabetes: a systematic review and meta-analysis. Sports Med 44:487–499Google Scholar
  147. 147.
    Sigal RJ, Kenny GP, Boule NG, Wells GA, Prud’homme D, Fortier M et al (2007) Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 147:357–369PubMedGoogle Scholar
  148. 148.
    Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, Kramer K et al (2010) Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 304:2253–2262PubMedCentralPubMedGoogle Scholar
  149. 149.
    Kemi OJ, Ellingsen O, Ceci M, Grimaldi S, Smith GL, Condorelli G et al (2007) Aerobic interval training enhances cardiomyocytes contractility and Ca2+ cycling by phosphorylation of CaMKII and Thr-17 of phospholamban. J Mol Cell Cardiol 43:354–361PubMedCentralPubMedGoogle Scholar
  150. 150.
    Kaurstad G, Alves MN, Kemi OJ, Rolim N, Hoydal MA, Wisloff H et al (2012) Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training. Eur J App Physiol 112:579–588Google Scholar
  151. 151.
    Bennett CE, Virginia L, Shearer J, Belke DD (2013) Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice. Life Sci 92:657–663PubMedGoogle Scholar
  152. 152.
    Belke DD (2011) Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in the heart. J App Physiol 111:157–162Google Scholar
  153. 153.
    Cox EJ, Marsh SA (2013) Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart. Cardiovas Diabetol 12:101Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lorna Daniels
    • 1
  • James R. Bell
    • 2
  • Lea M. D. Delbridge
    • 2
  • Fiona J. McDonald
    • 1
  • Regis R. Lamberts
    • 1
  • Jeffrey R. Erickson
    • 1
    Email author
  1. 1.Department of PhysiologyUniversity of OtagoDunedinNew Zealand
  2. 2.Department of PhysiologyUniversity of MelbourneMelbourneAustralia

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