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Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts

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Biochemistry of Diabetes and Atherosclerosis

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 42))

Abstract

Alteration in cardiac function is one of the hallmarks of diabetes and in late stage is manifested as a decrease in contractility. While it is established that the release of calcium ions from internal sarcoplasmic reticulum via type 2 ryanodine receptor calcium-release channels (RyR2) is vital for efficient contraction, the relationship between diabetes-induced decrease in cardiac performance and alterations in expression and/or function of RyR2 is not well delineated. The present study was designed to address this question and to determine whether changes to RyR2 induced by chronic diabetes could be minimized with insulin-treatment. When paced at 3.3 Hz (200 beats per minute), hearts from 8-week streptozotocin-induced diabetic rats showed decreased responsiveness to isoproterenol stimulation; +dT/dt and -dT/dt were 56.5 ± 11.4% and 42.1 ± 12.1% that of control, respectively. Hearts from 8-week diabetic rats expressed 51.2% less RyR2 than controls. In addition, RyR2 from diabetic rats also showed decreased ability to bind the specific ligand [3H]ryanodine (22.4 ± 1.8% less [3H]ryanodine per ug of RyR2 protein), suggesting dysfunction. Two-weeks of insulin treatment, initiated after 6 weeks of untreated diabetes was able to minimize loss in function and expression of RyR2. Taken collectively, these data suggest that the decrease in cardiac contractility induced by chronic diabetes results in part from decreases in expression and alteration in function of RyR2 and these changes could be attenuated with insulin treatment. (Mol Cell Biochem 249: 113–123, 2003)

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References

  1. Rubier S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A: New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 30: 595–560, 1972

    Article  Google Scholar 

  2. Asmal AC, Leary WP, Thandroyen FS: Diabetic heart disease. Afr Med J 57: 788–790, 1980

    CAS  Google Scholar 

  3. Regan TJ: Congestive heart failure in the diabetic. Annu Rev Med 34: 161–168, 1983

    Article  PubMed  CAS  Google Scholar 

  4. Hamby RI, Zoneraich S, Sherman S: Diabetic cardiomyopathy. JAMA 229: 1749–1754, 1974

    Article  PubMed  CAS  Google Scholar 

  5. Reagan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmad MR, Haider B: Evidence for cardiomyopathy in familiar diabetes mellitus. J Clin Invest 60: 885–899, 1977

    Article  Google Scholar 

  6. Mahgoub MA, Abd-Elfattah AS: Diabetes mellitus and cardiac function. Mol Cell Biochem 180: 59–64, 1998

    Article  PubMed  CAS  Google Scholar 

  7. Tahiliani AG, McNeill JH: Diabetes-induced abnormalities in the myocardium. Life Sci 38: 959–974, 1986

    Article  PubMed  CAS  Google Scholar 

  8. Takeda N, Dixon IM, Hata T, Elimban V, Shah KR, Dhalla NS: Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes. Diabetes Res Clin Pract 30(suppl): 113–122, 1996

    Article  PubMed  Google Scholar 

  9. Cheta D: Animal models of type I (insulin-dependent) diabetes mellitus. J Pediatr Endocrinol Metab 11: 11–19, 1998

    Article  PubMed  CAS  Google Scholar 

  10. Wong FS, Janeway CA Jr: Insulin-dependent diabetes mellitus and its animal models. Curr Opin Immunol 11: 643–647, 1999

    Article  PubMed  CAS  Google Scholar 

  11. Sarvetnick N: Transgenic models of diabetes. Curr Opin Immunol 2: 604–604, 1989/1990

    Article  PubMed  CAS  Google Scholar 

  12. Yamamura K, Miyazaki T, Uno M, Miyazaki J: Transgenic mouse as a tool for the study of autoimmune disease: Insulin-dependent diabetes mellitus. Int J Immunopharmacol 14: 451–455, 1992

    Article  PubMed  CAS  Google Scholar 

  13. Pierce GN, Maddaford TG, Russell JC: Cardiovascular dysfunction in insulin-dependent and non-insulin-dependent animal models of diabetes mellitus. Can J Physiol Pharmacol 75: 343–350, 1997

    Article  PubMed  CAS  Google Scholar 

  14. Paulson DJ, Tahiliani AG: Cardiovascular abnormalities associated with human and rodent obesity. Life Sci 51: 1557–1569, 1992

    Article  PubMed  CAS  Google Scholar 

  15. Dai S, Todd ME, Lee S, McNeill JH: Fructose loading induces cardiovascular and metabolic changes in non-diabetic and diabetic rats. Can J Physiol Pharmacol 72: 771–781, 1994

    Article  PubMed  CAS  Google Scholar 

  16. Trayhurn P: The development of obesity in animals: the role of genetic susceptibility. Clin Endocrinol Metab 13: 451–474, 1984

    Article  PubMed  CAS  Google Scholar 

  17. Clark J, Palmer C, Shaw W: The diabetic Zucker fatty rat. Proc Soc Exp Biol Med 173: 68–75, 1983

    PubMed  CAS  Google Scholar 

  18. van Zwieten PA: Diabetes and hypertension: Experimental models for pharmacological studies. Clin Exp Hypertens 21: 1–16, 1999

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Tahiliani AG, Vadlamudi RV, McNeill JH: Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. Can J Physiol Pharmacol 61: 516–523, 1983

    Article  PubMed  CAS  Google Scholar 

  21. Mihm MJ, Seifert JL, Coyle CM, Bauer JA: Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an experimental rat model. Life Sci 69: 527–542, 2001

    Article  PubMed  CAS  Google Scholar 

  22. Dincer UD, Bidasee KR, Guner S, Tay A, Ozcelikay AT, Altan VM: The effect of diabetes on expression of β1-, β2-, and β3-adrenoreceptors in rat hearts. Diabetes 50: 455–461, 2001

    Article  PubMed  CAS  Google Scholar 

  23. Bers DM: Excitation Contraction Coupling and Cardiac Contractile Force. Kluwer Academic Press, Boston, USA, 1991

    Google Scholar 

  24. Berridge MJ: Elementary and global aspects of calcium signalling. J Physiol (Lond) 499: 291–306, 1997

    CAS  Google Scholar 

  25. Yu Z, McNeill JH: Force-interval relationship and its response to ryanodine in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 69: 1268–1276, 1991

    Article  PubMed  CAS  Google Scholar 

  26. Yu Z, Tibbits GF, McNeill JH: Cellular functions of diabetic cardiomyocytes: Contractility, rapid-cooling contracture, and ryanodine binding. Am J Physiol 266: H2082–H2089, 1994

    PubMed  CAS  Google Scholar 

  27. Zhong Y, Ahmed S, Grupp IL, Matlib MA: Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts. Am J Physiol 281: H1137–H1147, 2001

    CAS  Google Scholar 

  28. Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS: Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart. Diabetes. 50: 2133–2138, ?year?

    Google Scholar 

  29. Bidasee KR, Dincer UD, Besch HR Jr: Ryanodine receptor dysfunction in hearts of streptozotocin-induced diabetic rats. Mol Pharmacol 60: 1356–1364, 2001

    PubMed  CAS  Google Scholar 

  30. Rodrigues B, Cam MC, McNeill JH: Metabolic disturbances in diabetic cardiomyopathy. Mol Cell Biochem 180: 53–57, 1998

    Article  PubMed  CAS  Google Scholar 

  31. Bidasee KR, Besch HR Jr, Kwon S, Emmick JT, Besch KT, Gerzon K: C10-Oeq N-(4-azido-5–125iodo salicyloyl)-β-alanyl-β-alanyl ryanodine, a novel photo-affinity ligand for the ryanodine binding site. J Labelled Comp Radiopharm 34: 33–47, 1994

    Article  Google Scholar 

  32. Watanabe AM, Besch HR Jr: Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium. Circ Res 37: 309–317, 1975

    Article  PubMed  CAS  Google Scholar 

  33. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  CAS  Google Scholar 

  34. Meissner G, el-Hashem A: Ryanodine as a functional probe of the skeletal muscle sarcoplasmic reticulum Ca2+ release channel. Mol Cell Biochem 114: 119–123, 1992

    Article  PubMed  CAS  Google Scholar 

  35. Chu A, Diaz-Munoz M, Hawkes MJ, Brush K, Hamilton SL: Ryanodine as a probe for the functional state of the skeletal muscle sarcoplasmic reticulum calcium release channel. Mol Pharmacol 37: 735–741, 1990

    PubMed  CAS  Google Scholar 

  36. Cheng Y-C, Prusoff WH: Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (150) of an enzymatic reaction. Biochem Pharmacol 22: 3099–3108, 1973

    Article  PubMed  CAS  Google Scholar 

  37. Russ M, Reinauer H, Eckel J: Diabetes-induced decrease in the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in adult rat cardiomyocytes. Biochem Biophys Res Commun 178: 906–912, 1991

    Article  PubMed  CAS  Google Scholar 

  38. Zarain-Herzberg A, Yano K, Elimban V, Dhalla NS: Cardiac sarcoplasmic reticulum Ca2+-ATPase expression in streptozotocin-induced diabetic rat heart. Biochem Biophys Res Commun 203: 113–120, 1994

    Article  PubMed  CAS  Google Scholar 

  39. Dhalla NS, Lui X, Panagia V, Takeda N: Subcellular remodeling and heart dysfunction in chronic diabetes. J Cardiovasc Res 40: 239–247, 1998

    Article  CAS  Google Scholar 

  40. Uusitupa MI, Mustonen JN, Airaksinen KE: Diabetic heart muscle disease. Ann Med 22: 377–386, 1990

    Article  PubMed  CAS  Google Scholar 

  41. Fein FS: Diabetic cardiomyopathy. Diabetes Care 13(suppl 4): 1169–1179, 1990

    Article  PubMed  CAS  Google Scholar 

  42. Bell DS: Diabetic cardiomyopathy. A unique entity or a complication of coronary artery disease. Diabetes Care 18: 708–714, 1995

    Article  PubMed  CAS  Google Scholar 

  43. Chatham JC, Forder JR, McNeill JH (eds): The Diabetic Heart. Kluwer Academic Press, Massachusetts, USA, 1996

    Google Scholar 

  44. Ferrington DA, Krainev AG, Bigelow DJ: Altered turnover of calcium regulatory proteins of the sarcoplasmic reticulum in aged skeletal muscle. J Biol Chem 273: 5885–5891, 1998

    Article  PubMed  CAS  Google Scholar 

  45. Brownlee M, Cerami A, Vlassara H: Advanced glycosylation end products in tissues and the biochemical basis of diabetic complications. N Engl J Med 319: 315–321, 1988

    Google Scholar 

  46. Bunn HF, Higgins PJ: Reactions of monosaccharides with proteins: Possible evolutionary significance. Science 213: 222–224, 1981

    Article  PubMed  CAS  Google Scholar 

  47. Bucala R, Cerami A: Advanced glycosylation: Chemistry, biology and implications for diabetes and aging. Adv Pharmacol 23: 1–34, 1992

    Article  PubMed  CAS  Google Scholar 

  48. Wolff SP, Jiang ZY, Hunt JV: Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 10: 339–352, 1991

    Article  PubMed  CAS  Google Scholar 

  49. Obereley LW: Free radical and diabetes. Free Radic Biol Med 5: 113–124, 1988

    Article  Google Scholar 

  50. Giugliano D, Ceriello A, Paolisso G: Oxidative stress and diabetic vascular complications. Diabetes Care 19: 257–267, 1996

    Article  PubMed  CAS  Google Scholar 

  51. Dhalla NS, Temsah RM, Netticadan T: Role of oxidative stress in cardiovascular diseases. J Hypertens 18: 655–673, 2000

    Article  PubMed  CAS  Google Scholar 

  52. Smogorzewski M, Galfayan V, Massry SG: High glucose concentration causes a rise in [Ca2+]i of cardiac myocytes. Kidney Int 53: 1237–1243, 1998

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA

    Keshore R. Bidasee, Karuna Nallani, Bruce Henry & Henry R. Besch Jr

  2. Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey

    U. Deniz Dincer

Authors
  1. Keshore R. Bidasee
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  2. Karuna Nallani
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  3. Bruce Henry
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  4. U. Deniz Dincer
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  5. Henry R. Besch Jr
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Editor information

Editors and Affiliations

  1. Division of Stroke Vascular Disease, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    James S. C. Gilchrist

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Center, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    Paramjit S. Tappia  & Thomas Netticadan  & 

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Bidasee, K.R., Nallani, K., Henry, B., Dincer, U.D., Besch, H.R. (2003). Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. In: Gilchrist, J.S.C., Tappia, P.S., Netticadan, T. (eds) Biochemistry of Diabetes and Atherosclerosis. Developments in Molecular and Cellular Biochemistry, vol 42. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9236-9_15

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  • DOI: https://doi.org/10.1007/978-1-4419-9236-9_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4852-8

  • Online ISBN: 978-1-4419-9236-9

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