Skip to main content
SpringerLink
Log in
Book cover

Biochemistry of Diabetes and Atherosclerosis pp 157–165Cite as

Impairment of glucose metabolism and energy transfer in the rat heart

  • Chapter

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

Abstract

The metabolic pathways involved in ATP production in hypertriglyceridemic rat hearts were evaluated. Hearts from male Wistar rats with sugar-induced hypertriglyceridemia were perfused in an isolated organ system. Mechanical performance, oxygen uptake and beat rate were evaluated under perfusion with different oxidizable substrates. Age- and weight-matched animals were used as control. The hypertriglyceridemic (HTG) hearts showed a decrease in the mechanical work and slight diminution in the oxygen uptake when perfused with glucose, pyruvate or lactate. No differences were found when perfused with palmitate, octanoate or β-hydroxybutyrate. The glycolytic flux in HTG hearts was 2.4 times lower than in control hearts. Phosphofructokinase-I (PFK-I) was 16% decreased in HTG hearts, whereas pyruvate kinase activity did not change. The increased levels of glucose-6-phosphate in HTG heart, suggested a flux limitation by the PFK-I. Pyruvate dehydrogenase in its active form (PDHa) diminished as well. The PDHa level in the HTG hearts was restored to control values by dichloroacetate; however, this addition did not significantly improve the mechanical performance. Levels of ATP and phosphocreatine as well as total creatine kinase activity and the MB fraction were significant lower in the HTG hearts perfused with glucose. The data suggested that supply of ATP by glucose oxidation did not suffice to support cardiac work in the HTG hearts; this impairment was exacerbated by the diminution of the creatine kinase system output. (Mol Cell Biochem 249: 157–165, 2003)

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Reaven GM, Ho H: Sugar-induced hypertension in Sprague-Dawley rats. Hypertension 4: 610–614, 1991

    CAS  Google Scholar 

  2. Antozzi C, Zeviani M: Cardiomyopathies in disorders of oxidative metabolism. Cardiovasc Res 35: 184–199, 1997

    Article  PubMed  CAS  Google Scholar 

  3. Reaven GM: Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension. Parallels between human disease and rodent models. Diabetes Care 14: 195–203, 1991

    Article  PubMed  CAS  Google Scholar 

  4. Banos G, Carvajal K, Cardoso G, Zamora J, Franco M: Vascular reactivity and effect of serum in a rat model of hypertriglyceridemia and hypertension. Am J Hypertens 10: 397–388, 1997

    Google Scholar 

  5. Carvajal K, El Hafidi M, Banos G: Myocardial damage due to ischemia and reperfusion in hypertriglyceridemic and hypertensive rats: Participation of free radicals and calcium overload. J Hypertens 17: 1607–1616, 1999

    Article  PubMed  CAS  Google Scholar 

  6. Carvajal K, Banos G: Myocardial function and effect of serum in isolated heart from hypertriglyceridemic and hypertensive rats. Clin Exp Hypertens 24: 235–248, 2002

    Article  PubMed  CAS  Google Scholar 

  7. Minhaz U, Koide S, Shohtsu A, Fujishima M, Nakazawa H: Perfusion delays causes unintentional ischemic preconditioning in isolated heart preparation. Basic Res Cardiol 90: 418–423, 1995

    Article  PubMed  CAS  Google Scholar 

  8. Döring JH, Denherd H: The isolated perfused warm blooded heart according to Langendorff. In: Methods in Experimental Physiology and Pharmacology. Biological Measurements Techniques. V. Biomesstechnik-Verlang Mars, Germany, 1988

    Google Scholar 

  9. Hansford RG, Castro F: Role of Ca2+ in pyruvate dehydrogenase interconversion in brain mitochondria and synaptosomes. Biochem J 227: 129–136, 1985

    PubMed  CAS  Google Scholar 

  10. Reinhart GD, Lardy HA: Rat liver phosphofructokinase: Kinetic activity on the near-physiological conditions. Biochemistry 19: 1477–1484, 1980

    Article  PubMed  CAS  Google Scholar 

  11. Lowry OH, Rosenbrough NJ, Ferr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 14: 425–449, 1951

    Google Scholar 

  12. Bergmeyer HU: In: Methods of Enzymatic Analysis, vol. III. Verlag Chemie, Weinheim, 1974, pp 1465–1473

    Google Scholar 

  13. Bergmeyer HU: In: Methods of Enzymatic Analysis, vol. VIII. Verlag Chemie, Weinheim, 1983, pp 500–514

    Google Scholar 

  14. Hansford RG, Hogue B, Prokopczuk A, Wasilewka E, Lewartowski B: Activation of pyruvate dehydrogenase by electrical stimulation, and low Na+ perfusion of Guinea-pig heart. Biochim Biophys Acta 1018: 282–286, 1990

    Article  PubMed  CAS  Google Scholar 

  15. Hansford RG, Cohen L: Relative importance of pyruvate dehydrogenase interconversion and feed-back inhibition in the effect of fatty acids on pyruvate oxidation by rat heart mitochondria. Arch Biochem Biophys 191: 65–81, 1978

    Article  PubMed  CAS  Google Scholar 

  16. Konecka A, Jezierski T: Effect of cholesterol-enriched diet on liver and heart enzymes in male rabbits. Comp Biochem Physiol B 118: 505–508, 1997

    Article  PubMed  CAS  Google Scholar 

  17. Hansford RG, Moreno-Sanchez R, Lewartowski B: Activation of pyruvate dehydrogenase complex by Ca2+ in intact heart, cardiac myocytes, and cardiac mitochondria. Ann NY Acad Sci 573: 240–253, 1989

    Article  PubMed  CAS  Google Scholar 

  18. Van der Vusse GJ, Dubelaar ML, Coumans WA, Seymor AML, Clarke SB, Bonen A, Drake-Holland AJ, Noble MIM: Metabolic alterations in the chronically denervated dog heart. Cardiovasc Res 37:160–170, 1998

    Article  PubMed  Google Scholar 

  19. Whitehouse S, Cooper RH, Randle PJ: Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids. Biochem J 141: 761–774, 1974

    PubMed  CAS  Google Scholar 

  20. Biinger R, Permanetter B: Parallel stimulation by Ca2+ of inotropism and pyruvate dehydrogenase in perfused heart. Am J Physiol 247: C45–C52, 1984

    Google Scholar 

  21. Shöder H, Knight RJ, Kofoed KF, Schelberrt HR, Buxton DB: Regulation of pyruvate dehydrogenase activity and glucose metabolism in post-ischaemic myocardium. Biochim Biophys Acta 1406: 62–72, 1998

    Article  Google Scholar 

  22. Nienaber CA, Gambhir SS, Mody FV, Ratib O, Huang SC: Regional myocardial blood flow and glucose utilization in symptomatic patients with hypertrophie cardiomyopathy. Circulation 87: 1580–1590, 1993

    Article  PubMed  CAS  Google Scholar 

  23. Sugden MC, Fryer LGD, Holness MJ: Regulation of hepatic pyruvate dehydrogenase kinase by insulin and dietary manipulation in vivo. Studies with the euglycaemic-hyperinsulinaemic clamp. Biochim Biophys Acta 1316: 114–120, 1996

    Article  PubMed  Google Scholar 

  24. Bessman SP, Geiger PJ: Transport of energy in muscle: The phosphorylcreatine shuttle. Science 211: 448–452, 1981

    Article  PubMed  CAS  Google Scholar 

  25. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberg HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: The ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281: 21–40, 1992

    PubMed  CAS  Google Scholar 

  26. Kammermeier H: Meaning of energetic parameters. Basic Res Cardiol 88: 380–384, 1993

    Article  PubMed  CAS  Google Scholar 

  27. Sellevold OFM, Jynge P, Arstad K: High performance liquid chromatography: A rapid isocratic method for determination of creatine compounds and adenine nucleotides in myocardial tissue. J Mol Cell Cardiol 18: 517–527, 1986

    Article  PubMed  CAS  Google Scholar 

  28. Neubauer S: Influence of left ventricular pressures and heart rate on myocardial high-energy phosphate metabolism. Basic Res Cardiol 93: 102–107, 1998

    Article  PubMed  Google Scholar 

  29. Rottenberg H: Decoupling of oxidative phosphorylation. Biochim Biophys Acta 1018: 1–17, 1990

    Article  PubMed  CAS  Google Scholar 

  30. Rodrigues B, McNeill JH: The diabetic heart. Metabolic causes for the development of a cardiomyopathy. Mol Cell Biochem 180: 53–57, 1998

    Article  PubMed  CAS  Google Scholar 

  31. Smolenski RT, Jayakumar J, Seymor ML, Yacoub MH: Energy metabolism and mechanical recovery after cardioplegia in moderately hypertrophied rats. Mol Cell Biochem 180: 137–143, 1998

    Article  PubMed  CAS  Google Scholar 

  32. Paulson DJ: Carnitine deficiency-induced cardiomyopathy. Mol Cell Biochem 180: 33–41, 1998

    Article  PubMed  CAS  Google Scholar 

  33. Jeffrey FMH, Siczku V, Sherry AD, Malloy CR: Substrate selection in the isolated working rat heart. effects of reperfusion, afterload, and concentration. Basic Res Cardiol 90: 388–396, 1995

    Article  PubMed  CAS  Google Scholar 

  34. Lucas DT, Szweda LI: Declines in mitochondrial respiration during cardiac reperfusion: Age-dependent inactivation of a-ketoglurarate dehydrogenase. Proc Natl Acad Sci USA 96: 6689–6693, 1999

    Article  PubMed  CAS  Google Scholar 

  35. Kalsi KK, Smolenski RT, Pritchard RD, Khaghani A, Seymour AML, Yacoub MH: Energetics and function of the failing human heart with dilated or hypertrophie cardiomyopathy. Eur J Clin Invest 29: 469–477, 1999

    Article  PubMed  CAS  Google Scholar 

  36. Hak JB, Van Beek HGM, Eijgelshoven MHJ, Westerhof N: Mitochondrial dehydrogenase activity affects adaptation of cardiac oxygen consumption to demand. Am J Physiol 264: H448–H453, 1993

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. El Alaoui-Talibi Z, Gurnouz A, Moravec M, Moravec J: Control of oxidative metabolism in volume-overloaded rat hearts: Effect of propionyl-L-carnitine. Am J Physiol 272: H1615–H1624, 1997

    Google Scholar 

  39. Goodwin GW, Taylor CS, Taegtmeyer H: Regulation of energy metabolism of the heart during acute increase in heart work. J Biol Chem 272: 29530–29539, 1998

    Article  Google Scholar 

  40. Katz LA, Swain JA, Portman MA, Balaban RS: Relation between phosphate metabolites and oxygen consumption of heart in vivo. Am J Physiol 25: H265–H274, 1989

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  42. Klimes Y, Vràna A, Kunes J, Sebökova E, Dobesovà Z, Stolba P, Zicha J: Hereditary hypertriglyceridemic rat: A new model of metabolic alterations in hypertension. Blood Pressure 4: 137–142, 1995

    Article  PubMed  CAS  Google Scholar 

  43. Jucker BM, Rennings JM, Cline G, Shulman GI: 13C and 31 PNMR studies on the effects of increases plasma free fatty acids on intramuscular glucose metabolism in the awake rat. J Biol Chem 272: 10464–10473, 1997

    Article  PubMed  CAS  Google Scholar 

  44. Kerbey AL, Randle PJ, Cooper RH, Whitehouse S, Pask HT, Denton RM: Regulation of pyruvate dehydrogenase in rat heart. Biochem J 154: 327–348, 1976

    PubMed  CAS  Google Scholar 

  45. Latipää PM, Peuhkurinen KJ, Hiltunen JK, Hassinen IE: Regulation of pyruvate dehydrogenase during infusion of fatty acids of varying chain lengths in the perfused rat heart. J Mol Cell Cardiol 17: 1161–1171, 1985

    Article  PubMed  Google Scholar 

  46. Harrison GJ, van Wijhe MH, de Groot B, Dijk FJ, van Beek HGM: CK: Inhibition accelerates transcytosolic energy signalling during rapid workload steps in isolated rabbit hearts. J Physiol 276: H134–H140, 1999

    CAS  Google Scholar 

  47. Starling RC, Hammer DF, Altschuld RA: Human myocardial ATP content and in vivo contractile function. Mol Cell Biochem 180: 171–177, 1998

    Article  PubMed  CAS  Google Scholar 

  48. Hayashi H, Iimuro M, Masumorto Y, Kaeko M: Effects of gammaglutamylcysteine ethyl ester on heart mitochondrial creatine kinase activity: Involvement of sulfhydryl groups. Eur J Pharmacol 349: 133–136, 1998

    Article  PubMed  CAS  Google Scholar 

  49. Mekhfi H, Veksler V, Mateo P, Maupoil V, Rchette L, Ventura-Clapier R: Creatine kinase is the main target of reactive oxygen species in cardiac myofibrils. Circ Res 78: 1016–1027, 1996

    Article  PubMed  CAS  Google Scholar 

  50. El Hafidi M, Baños G: In vivo plasma lipid oxidation in sugar-induced rat hypertriglyceridemia and hypertension. Hypertension 30: 624–662, 1997

    Article  Google Scholar 

  51. Janero DR, Hreniuk D, Sharif HM: Hydroperoxide-induced oxidative stress impairs heart muscle cell carbohydrate metabolism. Am J Physiol 266: C179–C188, 1994

    PubMed  CAS  Google Scholar 

  52. Neely JR, Morgan HE: Relationship between carbohydrate and lipid metabolism and the energy balance of the heart. Ann Rev Physiol 36: 413–459, 1974

    Article  CAS  Google Scholar 

  53. Cargnoni A, Ceconi C, Curello S, Benigno M, de Jong JW, Ferrari R: Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia. Mol Cell Biochem 160/161: 187–194, 1996

    Article  CAS  Google Scholar 

  54. Vanoverschelde JLJ, Janier MF, Bakke JS Marshall, Bergmann SR: Rate of glycolysis during ischemia determines extent of ischemic injury and functional recovery after reperfusion. Am J Physiol 36: H1785–H1794, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Instituto Nacional de Cardiología, Juan Badiano 1, Col sectión XVI, Tlalpan, México D.F., 14080, Mexico

    Karla Carvajal, Guadalupe Baños & Rafael Moreno-Sánchez

Authors
  1. Karla Carvajal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guadalupe Baños
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rafael Moreno-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

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  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Carvajal, K., Baños, G., Moreno-Sánchez, R. (2003). Impairment of glucose metabolism and energy transfer in the rat heart. 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_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9236-9_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4852-8

  • Online ISBN: 978-1-4419-9236-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation