Skip to main content
SpringerLink
Log in

Mechanisms of subcellular remodeling in heart failure due to diabetes

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

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.

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. Regan TJ, Ahmed S, Haider B, Moschos C, Weisse A (1994) Diabetic cardiomyopathy: experimental and clinical observations. N Engl J Med 91:776–778

    CAS  Google Scholar 

  2. Notkins AL (1979) The causes of diabetes. Sci Am 241:62–73

    CAS  PubMed  Google Scholar 

  3. Christlieb AR (1973) Diabetes and hypertensive vascular disease. Am J Cardiol 32:592–606

    CAS  PubMed  Google Scholar 

  4. Regan TJ (1983) Congestive heart failure in the diabetic. Ann Rev Med 34:161–168

    CAS  PubMed  Google Scholar 

  5. Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease. JAMA 241:2035–2038

    CAS  PubMed  Google Scholar 

  6. Shah S (1980) Cardiomyopathy in diabetes mellitus. Angiology 31:502–504

    Google Scholar 

  7. Factor SM, Okun EM, Minase T (1980) Capillary microaneurysms in the human diabetic heart. N Engl J Med 302:384–388

    CAS  PubMed  Google Scholar 

  8. Dhalla NS, Pierce GN, Innes IR, Beamish RE (1985) Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J Cardiol 1:263–281

    CAS  PubMed  Google Scholar 

  9. Opie LH (1968) Metabolism of the heart in health and disease. Part 1. Am Heart J 76:685–698

    CAS  PubMed  Google Scholar 

  10. Opie LH, Tansey MJ, Kennelly BM (1979) The heart in diabetic mellitus. Part 1. Biochemical basis for myocardial dysfunction. S Afr Med J 56:207–211

    CAS  PubMed  Google Scholar 

  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 65:613–623

    CAS  PubMed Central  PubMed  Google Scholar 

  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 131–161

    Google Scholar 

  13. Kutryk MJ, Pierce GN, Dhalla NS (1987) Alterations in heart and serum lysosomal activities in streptozotocin-induced diabetes. Basic Res Cardiol 82:271–278

    CAS  PubMed  Google Scholar 

  14. Müller AL, Dhalla NS (2012) Role of various proteases in cardiac remodeling and progression of heart failure. Heart Fail Rev 17:395–409

    PubMed  Google Scholar 

  15. Ganguly PK, Dhalla KS, Innes IR, Beamish RE, Dhalla NS (1986) Altered norepinephrine turnover and metabolism in diabetic cardiomyopathy. Circ Res 59:684–693

    CAS  PubMed  Google Scholar 

  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–E739

    CAS  PubMed  Google Scholar 

  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 317–326

    Google Scholar 

  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 18:386–394

    CAS  PubMed  Google Scholar 

  19. Dillman WH (1989) Diabetes and thyroid-hormone-induced changes in cardiac function and their molecular basis. Annu Rev Med 40:373–394

    Google Scholar 

  20. Christlieb AR, Underwood L (1979) Renin-angiotensin-aldosterone system, electrolyte homeostasis and blood pressure in alloxan diabetes. Am J Med Sci 277:295–303

    CAS  PubMed  Google Scholar 

  21. Fein FS, Sonnenblick EH (1985) Diabetic cardiomyopathy. Prog Cardiovasc Dis 25:255–270

    Google Scholar 

  22. Stanley WC, Lopaschuk GD, McCormack JG (1997) Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 34:25–33

    CAS  PubMed  Google Scholar 

  23. Pierce GN, Russell JC (1997) Regulation of intracellular Ca2+ in the heart during diabetes. Cardiovasc Res 34:41–47

    CAS  PubMed  Google Scholar 

  24. Feuvray D (1997) The regulation of intracellular pH in the diabetic myocardium. Cardiovasc Res 34:48–54

    CAS  PubMed  Google Scholar 

  25. Yu JZ, Rodrigues B, McNeill JH (1997) Intracellular calcium levels are unchanged in the diabetic heart. Cardiovasc Res 34:91–98

    CAS  PubMed  Google Scholar 

  26. Hayashi H, Noda N (1997) Cystolic Ca2+ concentration in diabetic rat myocytes. Cardiovasc Res 34:99–103

    CAS  PubMed  Google Scholar 

  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 34:157–167

    CAS  Google Scholar 

  28. Malhotra A, Sanghi V (1997) Regulation of contractile proteins in diabetic heart. Cardiovasc Res 34:34–40

    CAS  PubMed  Google Scholar 

  29. Schaffer SW, Ballard-Croft C, Boerth S, Allo SN (1997) Mechanisms underlying depressed Na+/Ca2+ exchanger activity in the diabetic heart. Cardiovasc Res 34:129–136

    CAS  PubMed  Google Scholar 

  30. Ganguly PK, Pierce GN, Dhalla NS (1987) Diabetic cardiomyopathy: membrane dysfunction and therapeutic strategies. J Appl Cardiol 2:323–338

    Google Scholar 

  31. Schaffer SW (1991) Cardiomyopathy associated with non-insulin-dependent diabetes. Mol Cell Biochem 107:1–20

    CAS  PubMed  Google Scholar 

  32. Dhalla NS, Liu X, Panagia V, Takeda N (1998) Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovasc Res 40:239–247

    CAS  PubMed  Google Scholar 

  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 100–142

  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 83:1071–1091

    CAS  PubMed  Google Scholar 

  35. Dhalla NS, Rangi S, Zieroth S, Xu Y-J (2012) Alterations in sarcoplasmic reticulum and mitochondrial functions in diabetic cardiomyopathy. Exptl Clin Cardiol 17:115–120

    Google Scholar 

  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)

  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–S122

    Google Scholar 

  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–S77

    CAS  Google Scholar 

  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 200:15–25

    CAS  PubMed  Google Scholar 

  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 27:308–323

    CAS  PubMed  Google Scholar 

  41. Pierce GN, Dhalla NS (1983) Sarcolemmal Na+–K+ ATPase activity in diabetic rat heart. Am J Physiol 245:C241–C247

    CAS  PubMed  Google Scholar 

  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 188:91–101

    CAS  PubMed  Google Scholar 

  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–E207

    CAS  PubMed  Google Scholar 

  44. Heyliger CE, Prakash A, McNeill JH (1987) Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus. Am J Physiol 252:H540–H544

    Google Scholar 

  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 4:97–101

    Google Scholar 

  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–H261

    CAS  PubMed  Google Scholar 

  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 180:85–93

    CAS  PubMed  Google Scholar 

  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 80:5412–5416

    CAS  PubMed  Google Scholar 

  49. Lee SL, Ostadalova I, Kolar F, Dhalla NS (1992) Alterations in Ca2+-channels during the development of diabetic cardiomyopathy. Mol Cell Biochem 109:173–179

    CAS  PubMed  Google Scholar 

  50. Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS (1983) Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244:E528–E535

    CAS  PubMed  Google Scholar 

  51. Penpargkul S, Fein F, Sonnenblick EH, Scheuer J (1981) Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol 13:303–309

    CAS  PubMed  Google Scholar 

  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–H976

    Google Scholar 

  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 61:439–448

    Google Scholar 

  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 15:1–5

    CAS  PubMed  Google Scholar 

  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–H2089

    CAS  PubMed  Google Scholar 

  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–H1408

    CAS  PubMed  Google Scholar 

  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–H920

    CAS  PubMed  Google Scholar 

  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 50:2133–2138

    CAS  PubMed  Google Scholar 

  59. Vasanji Z, Dhalla NS, Netticadan T (2004) Increased inhibition of SERCA2 by phospholamban in the type 1 diabetic heart. Mol Cell Biochem 261:245–249

    CAS  PubMed  Google Scholar 

  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 1638:273–277

    CAS  PubMed  Google Scholar 

  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–H1537

    CAS  PubMed  Google Scholar 

  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–H2194

    CAS  PubMed  Google Scholar 

  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–C1171

    CAS  PubMed  Google Scholar 

  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 17:1035–1043

    CAS  PubMed  Google Scholar 

  65. Dhalla NS, Wang X, Beamish RE (1996) Intracellular calcium handling in normal and failing hearts. Exptl Clin Cardiol 1:7–20

    Google Scholar 

  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–C100

    CAS  PubMed  Google Scholar 

  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 1:89–96

    Google Scholar 

  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 203:113–120

    CAS  PubMed  Google Scholar 

  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 232:57–62

    CAS  PubMed  Google Scholar 

  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 527:85–94

    CAS  PubMed  Google Scholar 

  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 61:21–27

    PubMed  Google Scholar 

  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 353–371

    Google Scholar 

  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 31:100–111

    CAS  PubMed  Google Scholar 

  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 82:828–834

    CAS  PubMed  Google Scholar 

  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 84:111–118

    CAS  PubMed  Google Scholar 

  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 299:5–18

    CAS  PubMed  Google Scholar 

  77. Luiken JJ (2009) Sarcolemmal fatty acid uptake vs. mitochondrial beta-oxidation as target to regress cardiac insulin resistance. Appl Physiol Nutr Metab 34:473–480

    Google Scholar 

  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 8:39

    PubMed Central  PubMed  Google Scholar 

  79. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Phys Rev 85:1093–1129

    CAS  Google Scholar 

  80. Rodrigues B, Cam MC, McNeill JH (1995) Myocardial substrate metabolism: implications for diabetic cardiomyopathy. J Mol Cell Cardiol 27:169–179

    CAS  PubMed  Google Scholar 

  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 53:2366–2374

    CAS  PubMed  Google Scholar 

  82. Carley AN, Severson DL (2005) Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biophys Acta 1734:112–126

    CAS  Google Scholar 

  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 47:598–604

    CAS  PubMed  Google Scholar 

  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 34:1249–1257

    Google Scholar 

  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 107:233–241

    Google Scholar 

  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 115:909–917

    CAS  PubMed  Google Scholar 

  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 109:121–130

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Kuo TH, Moore KH, Giacomelli F, Wiener J (1983) Defective oxidative metabolism of heart mitochondria from genetically diabetic mice. Diabetes 32:781–787

    CAS  PubMed  Google Scholar 

  89. Pierce GN, Dhalla NS (1985) Heart mitochondrial function in chronic experimental diabetes in rats. Can J Cardiol 1:48–54

    CAS  PubMed  Google Scholar 

  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–H202

    CAS  Google Scholar 

  91. Pierce GN, Dhalla NS (1981) Cardiac myofibrillar ATPase activity in diabetic rats. J Mol Cell Cardiol 13:1063–1069

    CAS  PubMed  Google Scholar 

  92. Pierce GN, Dhalla NS (1985) Mechanisms of the defect in cardiac myofibrillar function during diabetes. Am J Physiol 248:E170–E175

    CAS  PubMed  Google Scholar 

  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 32:985–996

    CAS  PubMed  Google Scholar 

  94. Dillmann WH (1980) Diabetes mellitus induces changes in cardiac myosin of the rat. Diabetes 29:579–582

    CAS  PubMed  Google Scholar 

  95. Dillmann WH (1982) Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. Metabolism 31:199–204

    CAS  PubMed  Google Scholar 

  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 49:1243–1250

    CAS  PubMed  Google Scholar 

  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–H1055

    CAS  PubMed  Google Scholar 

  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–E30

    CAS  PubMed  Google Scholar 

  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 29:455–463

    CAS  PubMed  Google Scholar 

  100. Liu X, Takeda N, Dhalla NS (1997) Myosin light chain phosphorylation in diabetic cardiomyopathy in rats. Metabolism 46:71–75

    CAS  PubMed  Google Scholar 

  101. Liu X, Takeda N, Dhalla NS (1996) Troponin I phosphorylation in heart homogenate from diabetic rat. Biochim Biophys Acta 1316:78–84

    PubMed  Google Scholar 

  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–E804

    CAS  PubMed  Google Scholar 

  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 77:610–618

    CAS  PubMed  Google Scholar 

  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 5:454–461

    CAS  PubMed  Google Scholar 

  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 114:1358–1363

    CAS  PubMed  Google Scholar 

  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 37:1181–1187

    CAS  PubMed  Google Scholar 

  107. Atkins FL, Dowell RT, Love S (1985) Beta-adrenergic receptors, adenylate cyclase activity, and cardiac dysfunction in the diabetic rat. J Cardiovasc Pharmacol 7:66–70

    CAS  PubMed  Google Scholar 

  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 27:2315–2325

    CAS  PubMed  Google Scholar 

  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 142:685–689

    CAS  PubMed  Google Scholar 

  110. Allo SN, Schaffer SW (1990) Defective sarcolemmal phosphorylation associated with noninsulin-dependent diabetes. Biochim Biophys Acta 1023:206–212

    CAS  PubMed  Google Scholar 

  111. Smith CI, Pierce GN, Dhalla NS (1984) Alterations in adenylate cyclase activity due to streptozotocin-induced diabetic cardiomyopathy. Life Sci 34:1223–1230

    CAS  PubMed  Google Scholar 

  112. Tappia PS, Asemu G, Aroutiounova N, Dhalla NS (2004) Defective sarcolemmal phospholipase C signaling in diabetic cardiomyopathy. Mol Cell Biochem 261:193–199

    CAS  PubMed  Google Scholar 

  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 24:215–225

    CAS  PubMed  Google Scholar 

  114. Ganguly PK, Rice KM, Panagia V, Dhalla NS (1984) Sarcolemmal phosphatidylethanolamine N-methylation in diabetic cardiomyopathy. Circ Res 55:504–512

    CAS  PubMed  Google Scholar 

  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 86:777–784

    CAS  PubMed Central  PubMed  Google Scholar 

  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 57:95–99

    CAS  Google Scholar 

  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 12:1092–1098

    CAS  PubMed  Google Scholar 

  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 92:214–222

    CAS  PubMed  Google Scholar 

  119. Guo Z, Xia Z, Yuen VG, McNeill JH (2007) Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. Metabolism 56:1363–1371

    CAS  PubMed  Google Scholar 

  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 132:69–80

    CAS  PubMed  Google Scholar 

  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 86:812–818

    CAS  PubMed  Google Scholar 

  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 167–181

    Google Scholar 

  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 411–426

    Google Scholar 

  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 16:380–387

    CAS  Google Scholar 

  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 29:2355–2362

    CAS  PubMed  Google Scholar 

  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 285:17–27

    CAS  PubMed  Google Scholar 

  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 310:93–102

    CAS  PubMed  Google Scholar 

  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 23:356–367

    PubMed  Google Scholar 

  129. Yoshimura M, Anzawa R, Mochizuki S (2008) Cardiac metabolism in diabetes mellitus. Curr Pharm Des 14:2521–2526

    CAS  PubMed  Google Scholar 

  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 40:496–505

    CAS  PubMed  Google Scholar 

  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 25:111–124

    CAS  PubMed  Google Scholar 

  132. Ostman J (1983) beta-adrenergic blockade and diabetes mellitus. A review. Acta Med Scand 672(Suppl):69–77

    CAS  Google Scholar 

  133. Afzal N, Ganguly PK, Dhalla KS, Pierce GN, Singal PK, Dhalla NS (1988) Beneficial effects of verapamil in diabetic cardiomyopathy. Diabetes 37:936–942

    CAS  PubMed  Google Scholar 

  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–E458

    CAS  PubMed  Google Scholar 

  135. Machackova J, Liu X, Lukas A, Dhalla NS (2004) Renin-angiotensin blockade attenuates cardiac myofibrillar remodeling in chronic diabetes. Mol Cell Biochem 261:271–278

    CAS  PubMed  Google Scholar 

  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 1084:141–154

    CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface Hospital Research, University of Manitoba, 351 Tache Avenue, Winnipeg, MB, R2H 2A6, Canada

    Naranjan S. Dhalla & Vijayan Elimban

  2. Department of Internal Medicine, Katsushika Medical Centre, Jikei University, Tokyo, Japan

    Nobuakira Takeda

  3. Holguin University Hospital, Holguin, Cuba

    Delfin Rodriguez-Leyva

Authors
  1. Naranjan S. Dhalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nobuakira Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Delfin Rodriguez-Leyva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijayan Elimban
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naranjan S. Dhalla.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dhalla, N.S., Takeda, N., Rodriguez-Leyva, D. et al. Mechanisms of subcellular remodeling in heart failure due to diabetes. Heart Fail Rev 19, 87–99 (2014). https://doi.org/10.1007/s10741-013-9385-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-013-9385-8

Keywords

Search

Navigation