Advertisement

Heart Failure Reviews

, Volume 19, Issue 1, pp 87–99 | Cite as

Mechanisms of subcellular remodeling in heart failure due to diabetes

  • Naranjan S. DhallaEmail author
  • Nobuakira Takeda
  • Delfin Rodriguez-Leyva
  • Vijayan Elimban
Article

Abstract

Diabetic cardiomyopathy is not only associated with heart failure but there also occurs a loss of the positive inotropic effect of different agents. It is now becoming clear that cardiac dysfunction in chronic diabetes is intimately involved with Ca2+-handling abnormalities, metabolic defects and impaired sensitivity of myofibrils to Ca2+ in cardiomyocytes. On the other hand, loss of the inotropic effect in diabetic myocardium is elicited by changes in signal transduction mechanisms involving hormone receptors and depressions in phosphorylation of various membrane proteins. Ca2+-handling abnormalities in the diabetic heart occur mainly due to defects in sarcolemmal Na+–K+ ATPase, Na+–Ca2+ exchange, Na+–H+ exchange, Ca2+-channels and Ca2+-pump activities as well as changes in sarcoplasmic reticular Ca2+-uptake and Ca2+-release processes; these alterations may lead to the occurrence of intracellular Ca2+ overload. Metabolic defects due to insulin deficiency or ineffectiveness as well as hormone imbalance in diabetes are primarily associated with a shift in substrate utilization and changes in the oxidation of fatty acids in cardiomyocytes. Mitochondria initially seem to play an adaptive role in serving as a Ca2+ sink, but the excessive utilization of long-chain fatty acids for a prolonged period results in the generation of oxidative stress and impairment of their function in the diabetic heart. In view of the activation of sympathetic nervous system and renin-angiotensin system as well as platelet aggregation, endothelial dysfunction and generation of oxidative stress in diabetes and blockade of their effects have been shown to attenuate subcellular remodeling, metabolic derangements and signal transduction abnormalities in the diabetic heart. On the basis of these observations, it is suggested that oxidative stress and subcellular remodeling due to hormonal imbalance and metabolic defects play a critical role in the genesis of heart failure during the development of diabetic cardiomyopathy.

Keywords

Sarcolemmal defects Ca2+-handling abnormalities Sarcoplasmic reticular defects Myofibrillar proteins Mitochondrial function Subcellular remodeling 

Notes

Acknowledgments

The infrastructure support for the work in this article was provided by the St. Boniface Hospital Research Foundation.

Conflict of interest

The authors have no conflict of interest with any funding agency.

References

  1. 1.
    Regan TJ, Ahmed S, Haider B, Moschos C, Weisse A (1994) Diabetic cardiomyopathy: experimental and clinical observations. N Engl J Med 91:776–778Google Scholar
  2. 2.
    Notkins AL (1979) The causes of diabetes. Sci Am 241:62–73PubMedGoogle Scholar
  3. 3.
    Christlieb AR (1973) Diabetes and hypertensive vascular disease. Am J Cardiol 32:592–606PubMedGoogle Scholar
  4. 4.
    Regan TJ (1983) Congestive heart failure in the diabetic. Ann Rev Med 34:161–168PubMedGoogle Scholar
  5. 5.
    Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease. JAMA 241:2035–2038PubMedGoogle Scholar
  6. 6.
    Shah S (1980) Cardiomyopathy in diabetes mellitus. Angiology 31:502–504Google Scholar
  7. 7.
    Factor SM, Okun EM, Minase T (1980) Capillary microaneurysms in the human diabetic heart. N Engl J Med 302:384–388PubMedGoogle Scholar
  8. 8.
    Dhalla NS, Pierce GN, Innes IR, Beamish RE (1985) Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J Cardiol 1:263–281PubMedGoogle Scholar
  9. 9.
    Opie LH (1968) Metabolism of the heart in health and disease. Part 1. Am Heart J 76:685–698PubMedGoogle Scholar
  10. 10.
    Opie LH, Tansey MJ, Kennelly BM (1979) The heart in diabetic mellitus. Part 1. Biochemical basis for myocardial dysfunction. S Afr Med J 56:207–211PubMedGoogle Scholar
  11. 11.
    Seager MJ, Singal PK, Orchard R, Pierce GN, Dhalla NS (1984) Cardiac cell damage: a primary myocardial disease in the streptozotocin induced cardiac diabetes. Br J Exp Pathol 65:613–623PubMedCentralPubMedGoogle Scholar
  12. 12.
    Golfman LS, Takeda N, Beamish RE, Dhalla NS (1995) Cardiac contractile failure and ultrastructural abnormalities during the development of diabetic cardiomyopathy. In: Dhalla NS, Beamish RE, Takeda N, Nagano M (eds) The failing heart. Lippincott-Raven Publishers, Philadelphia, pp 131–161Google Scholar
  13. 13.
    Kutryk MJ, Pierce GN, Dhalla NS (1987) Alterations in heart and serum lysosomal activities in streptozotocin-induced diabetes. Basic Res Cardiol 82:271–278PubMedGoogle Scholar
  14. 14.
    Müller AL, Dhalla NS (2012) Role of various proteases in cardiac remodeling and progression of heart failure. Heart Fail Rev 17:395–409PubMedGoogle Scholar
  15. 15.
    Ganguly PK, Dhalla KS, Innes IR, Beamish RE, Dhalla NS (1986) Altered norepinephrine turnover and metabolism in diabetic cardiomyopathy. Circ Res 59:684–693PubMedGoogle Scholar
  16. 16.
    Ganguly PK, Beamish RE, Dhalla KS, Innes IR, Dhalla NS (1987) Norepinephrine storage, distribution and release in diabetic cardiomyopathy. Am J Physiol 252:E734–E739PubMedGoogle Scholar
  17. 17.
    Goyal RK, Umrani DN, Bodiwala DN, Dhalla NS (2003) Usefulness of 5-HT2A receptor antagonists in diabetes. In: Pierce GN, Nagano M, Zahradka P, Dhalla NS (eds) Atherosclerosis, Hypertension and Diabetes. Kluwer Academic Publishers, Boston, pp 317–326Google Scholar
  18. 18.
    Hileeto D, Cukiernik M, Mukherjee S, Evans T, Barbin Y, Downey D et al (2002) Contributions of endothelin-1 and sodium hydrogen exchanger-1 in the diabetic myocardium. Diabetes Metab Res Rev 18:386–394PubMedGoogle Scholar
  19. 19.
    Dillman WH (1989) Diabetes and thyroid-hormone-induced changes in cardiac function and their molecular basis. Annu Rev Med 40:373–394Google Scholar
  20. 20.
    Christlieb AR, Underwood L (1979) Renin-angiotensin-aldosterone system, electrolyte homeostasis and blood pressure in alloxan diabetes. Am J Med Sci 277:295–303PubMedGoogle Scholar
  21. 21.
    Fein FS, Sonnenblick EH (1985) Diabetic cardiomyopathy. Prog Cardiovasc Dis 25:255–270Google Scholar
  22. 22.
    Stanley WC, Lopaschuk GD, McCormack JG (1997) Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 34:25–33PubMedGoogle Scholar
  23. 23.
    Pierce GN, Russell JC (1997) Regulation of intracellular Ca2+ in the heart during diabetes. Cardiovasc Res 34:41–47PubMedGoogle Scholar
  24. 24.
    Feuvray D (1997) The regulation of intracellular pH in the diabetic myocardium. Cardiovasc Res 34:48–54PubMedGoogle Scholar
  25. 25.
    Yu JZ, Rodrigues B, McNeill JH (1997) Intracellular calcium levels are unchanged in the diabetic heart. Cardiovasc Res 34:91–98PubMedGoogle Scholar
  26. 26.
    Hayashi H, Noda N (1997) Cystolic Ca2+ concentration in diabetic rat myocytes. Cardiovasc Res 34:99–103PubMedGoogle Scholar
  27. 27.
    Koltai MZ, Hadhazy P, Posa I, Kocsis E, Winkler G, Rosen P et al (1997) Characteristics of coronary endothelial dysfunction in experimental diabetes. Cardovasc Res 34:157–167Google Scholar
  28. 28.
    Malhotra A, Sanghi V (1997) Regulation of contractile proteins in diabetic heart. Cardiovasc Res 34:34–40PubMedGoogle Scholar
  29. 29.
    Schaffer SW, Ballard-Croft C, Boerth S, Allo SN (1997) Mechanisms underlying depressed Na+/Ca2+ exchanger activity in the diabetic heart. Cardiovasc Res 34:129–136PubMedGoogle Scholar
  30. 30.
    Ganguly PK, Pierce GN, Dhalla NS (1987) Diabetic cardiomyopathy: membrane dysfunction and therapeutic strategies. J Appl Cardiol 2:323–338Google Scholar
  31. 31.
    Schaffer SW (1991) Cardiomyopathy associated with non-insulin-dependent diabetes. Mol Cell Biochem 107:1–20PubMedGoogle Scholar
  32. 32.
    Dhalla NS, Liu X, Panagia V, Takeda N (1998) Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovasc Res 40:239–247PubMedGoogle Scholar
  33. 33.
    Dhalla NS, Golfman LS, Elimban V, Takeda N (1996) Remodelling of subcellular organelles during the development of diabetic cardiomyopathy. In: Chatham JC, Fodder JR, McNeill JH (eds) The heart in diabetes. Kluwer Academic Publishers, Boston, pp 100–142Google Scholar
  34. 34.
    Machackova J, Barta J, Dhalla NS (2005) Molecular defects in cardiac myofibrillar proteins due to thyroid hormone imbalance and diabetes. Can J Physiol Pharmacol 83:1071–1091PubMedGoogle Scholar
  35. 35.
    Dhalla NS, Rangi S, Zieroth S, Xu Y-J (2012) Alterations in sarcoplasmic reticulum and mitochondrial functions in diabetic cardiomyopathy. Exptl Clin Cardiol 17:115–120Google Scholar
  36. 36.
    Dhalla NS, Elimban V (2013) Mechanisms of sarcolemmal defects in cardiac dysfunction due to chronic diabetes. In: Kimchi A (ed) Proceedings of the 17th world congress on heart disease. Medimond, Bologna (in press)Google Scholar
  37. 37.
    Takeda N, Dixon IMC, Hata T, Elimban V, Shah KR, Dhalla NS (1996) Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes. Diabetes Res Clin Prac 30(Suppl):S113–S122Google Scholar
  38. 38.
    Golfman LS, Takeda N, Dhalla NS (1996) Cardiac membrane Ca2+-transport in alloxan-induced diabetes in rats. Diabetes Res Clin Prac 31(Suppl):S73–S77Google Scholar
  39. 39.
    Golfman L, Dixon IMC, Takeda N, Chapman D, Dhalla NS (1999) Differential changes in cardiac myofibrillar and sarcoplasmic reticular gene expression in alloxan-induced diabetes. Mol Cell Biochem 200:15–25PubMedGoogle Scholar
  40. 40.
    Louch WE, Stokke MK, Sjaastad I, Christensen G, Sejersted OM (2012) No rest for the weary: diastolic calcium homeostasis in the normal and failing myocardium. Physiology 27:308–323PubMedGoogle Scholar
  41. 41.
    Pierce GN, Dhalla NS (1983) Sarcolemmal Na+–K+ ATPase activity in diabetic rat heart. Am J Physiol 245:C241–C247PubMedGoogle Scholar
  42. 42.
    Golfman L, Dixon IMC, Takeda N, Lukas A, Dakshinamurti K, Dhalla NS (1998) Cardiac sarcolemmal Na+–Ca2+ exchange and Na+–K+ ATPase activities and gene expression in alloxan-induced diabetes in rats. Mol Cell Biochem 188:91–101PubMedGoogle Scholar
  43. 43.
    Makino N, Dhalla KS, Elimban V, Dhalla NS (1987) Sarcolemmal Ca2+ transport in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol 253:E202–E207PubMedGoogle Scholar
  44. 44.
    Heyliger CE, Prakash A, McNeill JH (1987) Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus. Am J Physiol 252:H540–H544Google Scholar
  45. 45.
    Borda E, Pascual J, Wald M, Sterin-Borda L (1988) Hypersensitivity to calcium associated with an increased sarcolemmal Ca2+-ATPase activity in diabetic heart. Can J Cardiol 4:97–101Google Scholar
  46. 46.
    Pierce GN, Ramjiawan B, Dhalla NS, Ferrari R (1990) Na+–H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. Am J Physiol 258:H255–H261PubMedGoogle Scholar
  47. 47.
    Dyck JR, Lopaschuk GD (1998) Glucose metabolism, H+ production and Na+/H+-exchanger mRNA levels in ischemic hearts from diabetic animals. Mol Cell Biochem 180:85–93PubMedGoogle Scholar
  48. 48.
    Pierce GN, Kutryk MJB, Dhalla NS (1983) Alterations in calcium binding and composition of the cardiac sarcolemmal membrane in chronic diabetes. Proc Natl Acad Sci USA 80:5412–5416PubMedGoogle Scholar
  49. 49.
    Lee SL, Ostadalova I, Kolar F, Dhalla NS (1992) Alterations in Ca2+-channels during the development of diabetic cardiomyopathy. Mol Cell Biochem 109:173–179PubMedGoogle Scholar
  50. 50.
    Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS (1983) Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244:E528–E535PubMedGoogle Scholar
  51. 51.
    Penpargkul S, Fein F, Sonnenblick EH, Scheuer J (1981) Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol 13:303–309PubMedGoogle Scholar
  52. 52.
    Lopaschuk GD, Tahiliani AG, Vadlamudi RV, Katz S, McNeill JH (1984) Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats. Am J Physiol 245:H969–H976Google Scholar
  53. 53.
    Lopaschuk GD, Katz S, McNeill JH (1984) The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines. Can J Physiol Pharmacol 61:439–448Google Scholar
  54. 54.
    Lopaschuk GD, Eibschutz B, Katz S, McNeill JH (1984) Depression of calcium transport in sarcoplasmic reticulum from diabetic rats: lack of involvement by specific regulatory mediators. Gen Pharmacol 15:1–5PubMedGoogle Scholar
  55. 55.
    Yu Z, Tibbits GF, McNeill JH (1994) Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding. Am J Physiol 266:H2082–H2089PubMedGoogle Scholar
  56. 56.
    Choi KM, Zhong Y, Hoit BD, Grupp IL, Hahn H, Dilly KW et al (2002) Defective intracellular Ca2+ signaling contributes to cardiomyopathy in Type 1 diabetic rats. Am J Physiol Heart Circ Physiol 283:H1398–H1408PubMedGoogle Scholar
  57. 57.
    Yaras N, Bilginoglu A, Vassort G, Turan B (2007) Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by angiotensin II receptor blockade. Am J Physiol Heart Circ Physiol 292:H912–H920PubMedGoogle Scholar
  58. 58.
    Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS (2001) Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart. Diabetes 50:2133–2138PubMedGoogle Scholar
  59. 59.
    Vasanji Z, Dhalla NS, Netticadan T (2004) Increased inhibition of SERCA2 by phospholamban in the type 1 diabetic heart. Mol Cell Biochem 261:245–249PubMedGoogle Scholar
  60. 60.
    Rastogi S, Sentex E, Elimban V, Dhalla NS, Netticadan T (2003) Elevated levels of protein phosphatase 1 and phosphatase 2A may contribute to cardiac dysfunction in diabetes. Biochim Biophys Acta 1638:273–277PubMedGoogle Scholar
  61. 61.
    Lagadic-Gossmann D, Buckler KJ, Le Prigent K, Feuvray D (1996) Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 270:H1529–H1537PubMedGoogle Scholar
  62. 62.
    Ishikawa T, Kajiwara H, Kurihara S (1999) Alterations in contractile properties and Ca2+ handling in streptozotocin-induced diabetic rat myocardium. Am J Physiol 277:H2185–H2194PubMedGoogle Scholar
  63. 63.
    Allo SN, Lincoln TM, Wilson GL, Green FJ, Watanabe AM, Schaffer SW (1991) Non-insulin-dependent diabetes-induced defects in cardiac cellular calcium regulation. Am J Physiol 260:C1165–C1171PubMedGoogle Scholar
  64. 64.
    Ligeti L, Szenczi O, Prestia CM, Szabo C, Horvath K, Marcsek ZL et al (2006) Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. Int J Mol Med 17:1035–1043PubMedGoogle Scholar
  65. 65.
    Dhalla NS, Wang X, Beamish RE (1996) Intracellular calcium handling in normal and failing hearts. Exptl Clin Cardiol 1:7–20Google Scholar
  66. 66.
    Chua BH, Long WM, Lautensack N, Lins JA, Morgan HE (1983) Effects of diabetes on cardiac lysosomes and protein degradation. Am J Physiol 245:C91–C100PubMedGoogle Scholar
  67. 67.
    Xu Y-J, Elimban V, Takeda S, Ren B, Takeda N, Dhalla NS (1996) Cardiac sarcoplasmic reticulum function and gene expression in chronic diabetes. Cardiovasc Pathobiol 1:89–96Google Scholar
  68. 68.
    Zarain-Herzberg A, Yano K, Elimban V, Dhalla NS (1994) Cardiac sarcoplasmic reticulum Ca2+-ATPase expression in streptozotocin-induced diabetic rat heart. Biochem Biophys Res Commun 203:113–120PubMedGoogle Scholar
  69. 69.
    Kato K, Lukas A, Chapman DC, Rupp H, Dhalla NS (2002) Differential effects of etomoxir treatment on cardiac Na+-K+ ATPase subunits in diabetic heart. Mol Cell Biochem 232:57–62PubMedGoogle Scholar
  70. 70.
    Hattori Y, Matsuda N, Kimura J, Ishitani T, Tamada A, Gando S et al (2000) Diminished function and expression of the cardiac Na+–Ca2+ exchanger in diabetic rats: implication in Ca2+ overload. J Physiol 527:85–94PubMedGoogle Scholar
  71. 71.
    Zhou BQ, Hu SJ, Wang GB (2006) The analysis of ultrastructure and gene expression of sarco/endoplasmic reticulum calcium handling proteins in alloxan-induced diabetic rat myocardium. Acta Cardiol 61:21–27PubMedGoogle Scholar
  72. 72.
    Netticadan T, Rastogi S, Chohan PK, Goyal RK, Dhalla NS (2003) Regulation of cardiac function in diabetes. In: Pierce GN, Nagano M, Zahradka P, Dhalla NS (eds) Atherosclerosis, hypertension and diabetes. Kluwer Academic Publishers, Boston, pp 353–371Google Scholar
  73. 73.
    Cook SA, Varela-Carver A, Mongillo M, Kleinert C, Khan MT, Leccisotti L et al (2010) Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. Eur Heart J 31:100–111PubMedGoogle Scholar
  74. 74.
    Osborn BA, Daar JT, Laddaga RA, Romano FD, Paulson DJ (1997) Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J Appl Physiol 82:828–834PubMedGoogle Scholar
  75. 75.
    Banerjee SK, McGaffin KR, Pastor-Soler NM, Ahmad F (2009) SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states. Cardiovasc Res 84:111–118PubMedGoogle Scholar
  76. 76.
    Coort SL, Bonen A, van der Vusse GJ, Glatz JF, Luiken JJ (2007) Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters. Mol Cell Biochem 299:5–18PubMedGoogle Scholar
  77. 77.
    Luiken JJ (2009) Sarcolemmal fatty acid uptake vs. mitochondrial beta-oxidation as target to regress cardiac insulin resistance. Appl Physiol Nutr Metab 34:473–480Google Scholar
  78. 78.
    van den Brom CE, Huisman MC, Vlasblom R, Boontje NM, Duijst S, Lubberink M et al (2009) Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography. Cardiovasc Diabetol 8:39PubMedCentralPubMedGoogle Scholar
  79. 79.
    Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Phys Rev 85:1093–1129Google Scholar
  80. 80.
    Rodrigues B, Cam MC, McNeill JH (1995) Myocardial substrate metabolism: implications for diabetic cardiomyopathy. J Mol Cell Cardiol 27:169–179PubMedGoogle Scholar
  81. 81.
    Mazumder PK, O’Neill BT, Roberts MW, Buchanan J, Yun UJ, Cooksey RC et al (2004) Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53:2366–2374PubMedGoogle Scholar
  82. 82.
    Carley AN, Severson DL (2005) Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biophys Acta 1734:112–126Google Scholar
  83. 83.
    Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C et al (2006) Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol 47:598–604PubMedGoogle Scholar
  84. 84.
    Finck BN, Kelly DP (2007) Peroxisome proliferator-activated receptor alpha (PPARalpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart. J Mol Cell Cardiol 34:1249–1257Google Scholar
  85. 85.
    Banke NH, Wende AR, Leone TC, O’Donnell JM, Abel ED, Kelly DP et al (2010) Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARalpha. Circ Res 107:233–241Google Scholar
  86. 86.
    Duncan JG, Fong JL, Medeiros DM, Finck BN, Kelly DP (2007) Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-alpha/PGC-1alpha gene regulatory pathway. Circulation 115:909–917PubMedGoogle Scholar
  87. 87.
    Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A et al (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109:121–130PubMedCentralPubMedGoogle Scholar
  88. 88.
    Kuo TH, Moore KH, Giacomelli F, Wiener J (1983) Defective oxidative metabolism of heart mitochondria from genetically diabetic mice. Diabetes 32:781–787PubMedGoogle Scholar
  89. 89.
    Pierce GN, Dhalla NS (1985) Heart mitochondrial function in chronic experimental diabetes in rats. Can J Cardiol 1:48–54PubMedGoogle Scholar
  90. 90.
    Flarsheim CE, Grupp IL, Matlib MA (1996) Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart. Am J Physiol Heart Circ Physiol 271:H192–H202Google Scholar
  91. 91.
    Pierce GN, Dhalla NS (1981) Cardiac myofibrillar ATPase activity in diabetic rats. J Mol Cell Cardiol 13:1063–1069PubMedGoogle Scholar
  92. 92.
    Pierce GN, Dhalla NS (1985) Mechanisms of the defect in cardiac myofibrillar function during diabetes. Am J Physiol 248:E170–E175PubMedGoogle Scholar
  93. 93.
    Depre C, Young ME, Ying J, Ahuja HS, Han Q, Garza N et al (2000) Streptozotocin-induced changes in cardiac gene expression in the absence of severe contractile dysfunction. J Mol Cell Cardiol 32:985–996PubMedGoogle Scholar
  94. 94.
    Dillmann WH (1980) Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes 29:579–582PubMedGoogle Scholar
  95. 95.
    Dillmann WH (1982) Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. Metabolism 31:199–204PubMedGoogle Scholar
  96. 96.
    Malhotra A, Penpargkul S, Fein FS, Sonnenblick EH, Scheuer J (1981) The effect of streptozotocin-induced diabetes in rats on cardiac contractile proteins. Circ Res 49:1243–1250PubMedGoogle Scholar
  97. 97.
    Malhotra A, Mordes JP, McDermott L, Schaible TF (1985) Abnormal cardiac biochemistry in spontaneously diabetic Bio-Breeding/Worcester rat. Am J Physiol 249:H1051–H1055PubMedGoogle Scholar
  98. 98.
    Schaffer SW, Mozaffari MS, Artman M, Wilson GL (1989) Basis for myocardial mechanical defects associated with non-insulin-dependent diabetes. Am J Physiol 256:E25–E30PubMedGoogle Scholar
  99. 99.
    Takeda N, Nakamura I, Hatanaka T, Ohkubo T, Nagano M (1988) Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats. Jpn Heart J 29:455–463PubMedGoogle Scholar
  100. 100.
    Liu X, Takeda N, Dhalla NS (1997) Myosin light chain phosphorylation in diabetic cardiomyopathy in rats. Metabolism 46:71–75PubMedGoogle Scholar
  101. 101.
    Liu X, Takeda N, Dhalla NS (1996) Troponin I phosphorylation in heart homogenate from diabetic rat. Biochim Biophys Acta 1316:78–84PubMedGoogle Scholar
  102. 102.
    Liu X, Wang J, Takeda N, Binaglia L, Panagia V, Dhalla NS (1999) Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes. Am J Physiol 277:E798–E804PubMedGoogle Scholar
  103. 103.
    Heyliger CE, Pierce GN, Singal PK, Beamish RE, Dhalla NS (1982) Cardiac alpha and beta adrenergic receptor alterations in diabetic cardiomyopathy. Basic Res Cardiol 77:610–618PubMedGoogle Scholar
  104. 104.
    Ingebretsen CG, Hawelu-Johnson C, Ingebretsen WR Jr (1983) Alloxan-induced diabetes reduces beta-adrenergic receptor number without affecting adenylate cyclase in rat ventricular membranes. J Cardiovasc Pharmacol 5:454–461PubMedGoogle Scholar
  105. 105.
    Sundaresan PR, Sharma VK, Gingold SI, Banerjee SP (1984) Decreased beta-adrenergic receptors in rat heart in streptozotocin-induced diabetes: role of thyroid hormones. Endocrinology 114:1358–1363PubMedGoogle Scholar
  106. 106.
    Nishio Y, Kashiwagi A, Kida Y, Kodama M, Abe N, Saeki Y et al (1988) Deficiency of cardiac beta-adrenergic receptor in streptozocin-induced diabetic rats. Diabetes 37:1181–1187PubMedGoogle Scholar
  107. 107.
    Atkins FL, Dowell RT, Love S (1985) Beta-adrenergic receptors, adenylate cyclase activity, and cardiac dysfunction in the diabetic rat. J Cardiovasc Pharmacol 7:66–70PubMedGoogle Scholar
  108. 108.
    Roth DA, White CD, Hamilton CD, Hall JL, Stanley WC (1995) Adrenergic desensitization in left ventricle from streptozotocin diabetic swine. J Mol Cell Cardiol 27:2315–2325PubMedGoogle Scholar
  109. 109.
    Shpakov AO, Kuznetsova LA, Plesneva SA, Bondareva VM, Guryanov IA, Vlasov GP et al (2006) Decrease in functional activity of G-proteins hormone-sensitive adenylate cyclase signaling system, during experimental type II diabetes mellitus. Bull Exp Biol Med 142:685–689PubMedGoogle Scholar
  110. 110.
    Allo SN, Schaffer SW (1990) Defective sarcolemmal phosphorylation associated with noninsulin-dependent diabetes. Biochim Biophys Acta 1023:206–212PubMedGoogle Scholar
  111. 111.
    Smith CI, Pierce GN, Dhalla NS (1984) Alterations in adenylate cyclase activity due to streptozotocin-induced diabetic cardiomyopathy. Life Sci 34:1223–1230PubMedGoogle Scholar
  112. 112.
    Tappia PS, Asemu G, Aroutiounova N, Dhalla NS (2004) Defective sarcolemmal phospholipase C signaling in diabetic cardiomyopathy. Mol Cell Biochem 261:193–199PubMedGoogle Scholar
  113. 113.
    Okumura K, Ogawa K, Satake T (1983) Phospholipid methylation in canine cardiac membranes. Relations to beta-adrenergic receptors and digitalis receptors. Jpn Heart J 24:215–225PubMedGoogle Scholar
  114. 114.
    Ganguly PK, Rice KM, Panagia V, Dhalla NS (1984) Sarcolemmal phosphatidylethanolamine N-methylation in diabetic cardiomyopathy. Circ Res 55:504–512PubMedGoogle Scholar
  115. 115.
    Panagia V, Taira Y, Ganguly PK, Tung S, Dhalla NS (1990) Alterations in phospholipid N-methylation of cardiac subcellular membranes due to experimentally-induced diabetes in rats. J Clin Invest 86:777–784PubMedCentralPubMedGoogle Scholar
  116. 116.
    Williams SA, Tappia PS, Yu C-H, Binaglia L, Panagia V, Dhalla NS (1997) Subcellular alterations in cardiac phospholipase D in chronic diabetes. Prost Leukotr Essen Fatty Acids 57:95–99Google Scholar
  117. 117.
    Xu Y-J, Botsford MW, Panagia V, Dhalla NS (1996) Responses of heart function and intracellular free Ca2+ to phosphatidic acid in chronic diabetes. Can J Cardiol 12:1092–1098PubMedGoogle Scholar
  118. 118.
    Kuwahara Y, Yanagishita T, Konno N, Katagiri T (1997) Changes in microsomal membrane phospholipids and fatty acids and in activities of membrane-bound enzyme in diabetic rat heart. Basic Res Cardiol 92:214–222PubMedGoogle Scholar
  119. 119.
    Guo Z, Xia Z, Yuen VG, McNeill JH (2007) Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. Metabolism 56:1363–1371PubMedGoogle Scholar
  120. 120.
    Rupp H, Elimban V, Dhalla NS (1994) Modification of myosin isozymes and SR Ca2+-pump ATPase of the diabetic rat heart by lipid lowering interventions. Mol Cell Biochem 132:69–80PubMedGoogle Scholar
  121. 121.
    Kato K, Chapman DC, Rupp H, Lukas A, Dhalla NS (1999) Alterations of heart function and Na+–K+ ATPase activity by etomoxir in diabetic rats. J Appl Physiol 86:812–818PubMedGoogle Scholar
  122. 122.
    Ferrari R, Shah KR, Hata T, Beamish RE, Dhalla NS (1991) Subcellular defects in diabetic myocardium: Influence of propionyl L-carnitine on Ca2+-transport. In: Nagano M, Dhalla NS (eds) The diabetic heart. Raven Press, New York, pp 167–181Google Scholar
  123. 123.
    Dhalla NS, Dixon IMC, Shah KR, Ferrari R (1991) Beneficial effects of L-carnitine and derivatives on heart membranes in experimental diabetes. In: Ferrari R, DiMauro S, Sherwood G (eds) L-carnitine and its role in medicine: from function to therapy. Academic Press, London, pp 411–426Google Scholar
  124. 124.
    Goyal RK, Elimban V, Xu Y-J, Kumamoto H, Takeda N, Dhalla NS (2011) Mechanism of sarpogrelate action in improving cardiac function in diabetes. J Cardiovasc Pharmacol Therap 16:380–387Google Scholar
  125. 125.
    Kopp SJ, Daar J, Paulson DJ, Romano FD, Laddaga R (1997) Effects of oral vanadyl treatment on diabetes-induced alterations in the heart GLUT-4 transporter. J Mol Cell Cardiol 29:2355–2362PubMedGoogle Scholar
  126. 126.
    Siddiqui MR, Moorthy K, Taha A, Hussain ME, Baquer NZ (2006) Low doses of vanadate and Trigonella synergistically regulate Na+/K+-ATPase activity and GLUT4 translocation in alloxan-diabetic rats. Mol Cell Biochem 285:17–27PubMedGoogle Scholar
  127. 127.
    Vial G, Dubouchaud H, Couturier K, Lanson M, Leverve X, Demaison L (2008) Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes. Mol Cell Biochem 310:93–102PubMedGoogle Scholar
  128. 128.
    Chen S, Khan ZA, Karmazyn M, Chakrabarti S (2007) Role of endothelin-1, sodium hydrogen exchanger-1 and mitogen activated protein kinase (MAPK) activation in glucose-induced cardiomyocyte hypertrophy. Diabetes Metab Res Rev 23:356–367PubMedGoogle Scholar
  129. 129.
    Yoshimura M, Anzawa R, Mochizuki S (2008) Cardiac metabolism in diabetes mellitus. Curr Pharm Des 14:2521–2526PubMedGoogle Scholar
  130. 130.
    Gerbi A, Barbey O, Raccah D, Coste T, Jamme I, Nouvelot A et al (1997) Alteration of Na, K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats. Diabetologia 40:496–505PubMedGoogle Scholar
  131. 131.
    Vlkovicova J, Javorkova V, Stefek M, Kysel’ova Z, Gajdosikova A, Vrbjar N (2006) Effect of the pyridoindole antioxidant stobadine on the cardiac Na(+), K(+)-ATPase in rats with streptozotocin-induced diabetes. Gen Physiol Biophys 25:111–124PubMedGoogle Scholar
  132. 132.
    Ostman J (1983) beta-adrenergic blockade and diabetes mellitus. A review. Acta Med Scand 672(Suppl):69–77Google Scholar
  133. 133.
    Afzal N, Ganguly PK, Dhalla KS, Pierce GN, Singal PK, Dhalla NS (1988) Beneficial effects of verapamil in diabetic cardiomyopathy. Diabetes 37:936–942PubMedGoogle Scholar
  134. 134.
    Afzal N, Pierce GN, Elimban V, Beamish RE, Dhalla NS (1989) Influence of verapamil on some subcellular defects in diabetic cardiomyopathy. Am J Physiol 256:E453–E458PubMedGoogle Scholar
  135. 135.
    Machackova J, Liu X, Lukas A, Dhalla NS (2004) Renin-angiotensin blockade attenuates cardiac myofibrillar remodeling in chronic diabetes. Mol Cell Biochem 261:271–278PubMedGoogle Scholar
  136. 136.
    Liu X, Suzuki H, Sethi R, Tappia PS, Takeda N, Dhalla NS (2006) Blockade of renin-angiotensin system attenuates sarcolemma and sarcoplasmic reticulum remodeling in chronic diabetes. Ann New York Acad Sci 1084:141–154Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Naranjan S. Dhalla
    • 1
    Email author
  • Nobuakira Takeda
    • 2
  • Delfin Rodriguez-Leyva
    • 3
  • Vijayan Elimban
    • 1
  1. 1.Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface Hospital ResearchUniversity of ManitobaWinnipegCanada
  2. 2.Department of Internal Medicine, Katsushika Medical CentreJikei UniversityTokyoJapan
  3. 3.Holguin University HospitalHolguinCuba

Personalised recommendations