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High dietary sucrose triggers hyperinsulinemia, increases myocardial β-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery

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Abstract

Although the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate × pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, β-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii)␣increased β-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac β-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac β-oxidation but reduced glycolytic and lactate flux.

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References

  1. Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia Nutr Metab (Lond) 2: 5, 2005

    Article  CAS  Google Scholar 

  2. Mcauley KA, Hopkins CM, Smith KJ, Mclay RT, Williams SM, Taylor RW, Mann JL (2005) Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women Diabetologia 48: 8–16

    Article  PubMed  CAS  Google Scholar 

  3. Winitz M, Graff J, Seedman DA (1964) Effect of dietary carbohydrate on serum cholesterol levels Arch Biochem Biophys 108: 576–579

    Article  PubMed  CAS  Google Scholar 

  4. Winitz M, Seedman DA, Graff J (1970) Studies in metabolic nutrition employing chemically defined diets. I. Extended feeding of normal human adult males Am J Clin Nutr 23: 525–545

    PubMed  CAS  Google Scholar 

  5. Zavaroni I, Chen YD, Reaven GM (1982) Studies of the mechanism of fructose-induced hypertriglyceridemia in the rat Metabolism 31: 1077–1083

    Article  PubMed  CAS  Google Scholar 

  6. Guo X, Cheng S, Taylor KD, Cui J, Hughes R, Quinones MJ, Bulnes-Enriquez I, De la Rosa R, Aurea G, Yang H, Hsueh W, Rotter JI (2005) Hypertension genes are genetic markers for insulin sensitivity and resistance Hypertension 45: 799–803

    Article  PubMed  CAS  Google Scholar 

  7. Xi S, Yin W, Wang Z, Kusunoki M, Lian X, Koike T, Fan J, Zhang Q (2004) A minipig model of high-fat/high-sucrose diet-induced diabetes and atherosclerosis Int J Exp Pathol 85: 223–231

    Article  PubMed  Google Scholar 

  8. Streja D (2004) Metabolic syndrome and other factors associated with increased risk of diabetes Clin Cornerstone 6: S14–S29

    Article  PubMed  Google Scholar 

  9. Lempiainen P, Mykkanen L, Pyorala K, Laakso M, Kuusisto J (1999) Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men Circulation 100: 123–128

    PubMed  CAS  Google Scholar 

  10. Mangrum A, Bakris GL (1997) Predictors of renal and cardiovascular mortality in patients with non-insulin-dependent diabetes: a brief overview of microalbuminuria and insulin resistance J Diabetes Compl 11: 352–357

    Article  CAS  Google Scholar 

  11. Scheepers A, Joost HG, Schurmann A (2004) The glucose transporter families SGLT and GLUT: molecular basis of normal and aberrant function J Parenter Enteral Nutr 28: 364–371

    CAS  Google Scholar 

  12. Morel S, Berthonneche C, Tanguy S, Toufektsian MC, Foulon T, De Lorgeril M, de Leiris J, Boucher F (2003) Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats Clin Exp Pharmacol Physiol 30: 446–451

    Article  PubMed  CAS  Google Scholar 

  13. Gutman RA, Basilico MZ, Bernal CA, Chicco A, Lombardo YB (1987) Long-term hypertriglyceridemia and glucose intolerance in rats fed chronically an isocaloric sucrose-rich diet Metabolism 36: 1013–1020

    Article  PubMed  CAS  Google Scholar 

  14. Segal S, Lloyd S, Sherman N, Sussman K, Draznin B (1990) Postprandial changes in cytosolic free calcium and glucose uptake in adipocytes in obesity and non-insulin-dependent diabetes mellitus Horm Res 34: 39–44

    Article  PubMed  CAS  Google Scholar 

  15. Jang YJ, Ryu HJ, Choi YO, Kim C, Leem CH, Park CS (2002) Improvement of insulin sensitivity by chelation of intracellular Ca(2+) in high-fat-fed rats Metabolism 51: 912–918

    Article  PubMed  CAS  Google Scholar 

  16. Jang YJ, Ryu HJ, Choi YO, Lee JG, Kim C, Leem CH, Park CS (2004) Effects of an intracellular Ca(2+) chelator on insulin resistance and hypertension in high-fat-fed rats and spontaneously hypertensive rats Metabolism 53: 269–272

    Article  PubMed  CAS  Google Scholar 

  17. Benzi RH, Lerch R (1992) Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administred during reperfusion Circ Res 71: 567–576

    PubMed  CAS  Google Scholar 

  18. Du Toit E, Opie L (1992) Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at onset of reperfusion Circ Res 70: 960–967

    PubMed  CAS  Google Scholar 

  19. Desrois M, Sidell RJ, Gauguier D, Davey CL, Radda GK, Clarke K (2004) Gender differences in hypertrophy, insulin resistance and ischemic injury in the aging type 2 diabetic rat heart J Mol Cell Cardiol 37: 547–555

    Article  PubMed  CAS  Google Scholar 

  20. Jordan JE, Simandle SA, Tulbert CD, Busija DW, Miller AW (2003) Fructose-fed rats are protected against ischemia/reperfusion injury J Pharmacol Exp Ther 307: 1007–1011

    Article  PubMed  CAS  Google Scholar 

  21. Kristiansen SB, Lofgren B, Stottrup NB, Khatir D, Nielsen-Kudsk JE, Nielsen TT, Botker HE, Flyvbjerg A (2004) Ischaemic preconditioning does not protect the heart in obese and lean animal models of type 2 diabetes Diabetologia 47: 1716–1721

    Article  PubMed  CAS  Google Scholar 

  22. Sidell RJ, Cole MA, Draper NJ, Desrois M, Buckingham RE, Clarke K (2002) Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the Zucker fatty rat heart Diabetes 51: 1110–1117

    PubMed  CAS  Google Scholar 

  23. Wang P, Chatham JC (2004) Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart Am J Physiol 286: E725–E736

    Article  CAS  Google Scholar 

  24. Longnus SL, Wambolt RB, Barr RL, Lopaschuk GD, Allard MF (2001) Regulation of myocardial fatty acid oxidation by substrate supply Am J Physiol 281: H1561–H1567

    CAS  Google Scholar 

  25. Dangin M, Desport JC, Gachon P, Beaufrère B (1999) Rapid and accurate 13CO2 isotopic measurement in whole blood: comparison with expired gas Am J Physiol 276: E212–E216

    PubMed  CAS  Google Scholar 

  26. Bergmeyer HU: In: HU Bergmeyer (ed), Methods of enzymatic analysis, Vol. 3. New York, Verlag Chemie Weiheim, 1974

  27. Francis GA, Anicotte JS, Auwerx J (2003) PPAR-a effects on the heart and other vascular tissues Am J Physiol 285: H1–H9

    CAS  Google Scholar 

  28. Poizat C, Grably S, Cuchet P, Keriel C (1996) Relationship between heart function and energy production. A study on isolated rat heart. Arch Physiol Biochem 104: 71–80

    Article  PubMed  CAS  Google Scholar 

  29. Dowell RT, Atkins FL, Love S (1986) Integrative nature and time course of cardiovascular alterations in the diabetic rat J Cardiovasc Pharmacol 8: 406–413

    PubMed  CAS  Google Scholar 

  30. Hicks KK, Seifen E, Stimers JR, Kennedy RH (1998) Effects of streptozotocin-induced diabetes on heart rate, blood pressure and cardiac autonomic nervous control J Auton Nerv Syst 69: 21–30

    Article  PubMed  CAS  Google Scholar 

  31. James JH, Wagner KR, King JK, Leffler RE, Upputuri RK, Balasubramaniam A, Friend LA, Shelly DA, Paul RJ, Fischer JE (1999) Stimulation of both aerobic glycolysis and Na(+)-K(+)-ATPase activity in skeletal muscle by epinephrine or amylin Am J Physiol 277: E176–E186

    PubMed  CAS  Google Scholar 

  32. Maeda CY, Fernandes TG, Timm HB, Irigoyen MC (1995) Autonomic dysfunction in short-term experimental diabetes Hypertension 26: 1100–1104

    PubMed  CAS  Google Scholar 

  33. Oliveira VL, Moreira ED, Farah VD, Consolim-Colombo F, Krieger EM, Irigoyen MC (1999) Cardiopulmonary reflex impairment in experimental diabetes in rats Hypertension 34: 813–817

    PubMed  CAS  Google Scholar 

  34. Patel KP, Zhang PL (1995) Baroreflex function in streptozotocin (STZ) induced diabetic rats Diabetes Res Clin Pract 27: 1–9

    Article  PubMed  CAS  Google Scholar 

  35. Ramanadham S, Tenner TE (1986) Chronic effects of streptozotocin diabetes on myocardial sensitivity in the rat Diabetologia 29: 741–748

    Article  PubMed  CAS  Google Scholar 

  36. Saiki C, Seki N, Furuya H, Matsumoto S (2005) The acute effects of insulin on the cardiorespiratory responses to hypoxia in streptozotocin-induced diabetic rats Acta Physiol Scand 183: 107–115

    Article  PubMed  CAS  Google Scholar 

  37. Schaan BD, Dall’ago P, Maeda CY, Ferlin E, Fernandes TG, Schmid H, Irigoyen MC (2004) Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats Braz J Med Biol Res 37: 1895–1902

    Article  PubMed  CAS  Google Scholar 

  38. Luchette FA, Friend LA, Brown CC, Upputuri RK, James JH (1998) Increased skeletal muscle Na+, K+-ATPase activity as a cause of increased lactate production after hemorrhagic shock J Trauma 44: 796–801

    Article  PubMed  CAS  Google Scholar 

  39. Mccarter FD, James JH, Luchette FA, Wang L, Friend LA, King JK, Evans JM, George MA, Fischer JE (2001) Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage J Surg Res 99: 235–244

    Article  PubMed  CAS  Google Scholar 

  40. Novel-Chate V, Rey V, Chiolero R, Schneiter P, Leverve X, Jequier E, Tappy L (2001) Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle Am J Physiol 280: E296–E300

    CAS  Google Scholar 

  41. Paul RJ, Bauer M, Pease W (1979) Vascular smooth muscle: aerobic glycolysis linked to sodium and potassium transport processes Science 206: 1414–1416

    Article  PubMed  CAS  Google Scholar 

  42. Pierce GN, Philipson KD (1985) Binding of glycolytic enzymes to cardiac sarcolemmal and sarcoplasmic reticular membranes J Biol Chem 260: 6862–6870

    PubMed  CAS  Google Scholar 

  43. Weiss J, Hiltbrand B (1985) Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart J Clin Invest 75: 436–447

    Article  PubMed  CAS  Google Scholar 

  44. Weiss JN, Lamp ST (1989) Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis J Gen Physiol 94: 911–935

    Article  PubMed  CAS  Google Scholar 

  45. Xu KY, Zweier JL, Becker LC (1995) Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport Circ Res 77: 88–97

    PubMed  CAS  Google Scholar 

  46. Babick AP, Cantor EJ, Babick JT, Takeda N, Dhalla NS, Netticadan T (2004) Cardiac contractile dysfunction in j2n-k cardiomyopathic hamsters is associated with impaired SR function and regulation Am J Physiol 287: C1202–C1208

    Article  CAS  Google Scholar 

  47. Narayanan N, Yang C, Xu A (2004) Dexamethasone treatment improves sarcoplasmic reticulum function and contractile performance in aged myocardium Mol Cell Biochem 266: 31–36

    Article  PubMed  CAS  Google Scholar 

  48. Suarez J, Gloss B, Belke DD, Hu Y, Scott B, Dieterle T, Kim YK, Valencik ML, McDonald JA, Dillmann WH (2004) Doxycycline inducible expression of SERCA2a improves calcium handling and reverts cardiac dysfunction in pressure overload-induced cardiac hypertrophy Am J Physiol 287: H2164–H2172

    CAS  Google Scholar 

  49. Rupp H, Maisch B: Radiotelemetric characterization of overweight-associated rises in blood pressure and heart rate. Am J Physiol 277:H1540–H1545, 1999

    Google Scholar 

  50. Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, Delerive P, Fadel A, Chinetti G, Fruchart JC, Najib J, Maclouf J, Tedgui A (1998) Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not PPARgamma activators Nature 393: 790–793

    Article  PubMed  CAS  Google Scholar 

  51. Fujino T, Ishii Y, Takeuchi T, Hirasawa K, Tateda K, Kikuchi K, Hasebe N (2003) Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction Circ J 67: 757–762

    Article  PubMed  CAS  Google Scholar 

  52. Lopaschuk GD (1997) Alterations in fatty acid oxidation during reperfusion of the heart after myocardial ischemia Am J Cardiol 80: 11A–16A

    Article  PubMed  CAS  Google Scholar 

  53. Burkhoff D, Weiss RG, Schulman SP, Kalil-Filho R, Wannenburg T, Gerstenblith G (1991) Influence of metabolic substrate on rat heart function and metabolism at different coronary flow Am J Physiol 261: H741–H750

    PubMed  CAS  Google Scholar 

  54. Dyck JR, Cheng JF, Stanley WC, Barr R, Chandler MP, Brown S, Wallace D, Arrhenius T, Harmon C, Yang G, Nadzan AM, Lopaschuk GD (2004) Malonyl coenzyme A decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation Circ Res 94: E78–E84

    Article  PubMed  CAS  Google Scholar 

  55. Robergs RA (2001) Exercise-induced metabolic acidosis: where do the protons come from? Sports Sci 5: 1–20

    Google Scholar 

  56. Sentex E, Laurent A, Martine L, Grégoire S, Rochette L, Demaison L (1999) Calcium- and ADP-magnesium-induced uncoupling in isolated cardiac mitochondria: influence of cyclosporine A Mol Cell Biochem 202: 73–84

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the French National Institute for Agronomical Research.

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Authors and Affiliations

  1. Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM E221, Université J. Fourier, BP 53, 38041, Grenoble cedex 09, France

    D. Gonsolin, K. Couturier, B. Garait, S. Rondel, V. Novel-Chaté, S. Peltier, C. Keriel, R. Favier, L. Demaison & X. Leverve

  2. Département de Biologie Intégrée, CHU A. Michallon, 4ème étage, BP217, 38043, Grenoble cedex 09, France

    P. Faure

  3. Laboratoire de Nutrition Humaine, UMPE, INRA/Université d’Auvergne, 58 rue Montalembert, 63009, Clermont-Ferrand, France

    P. Gachon & Y. Boirie

  4. Laboratory of Cardiac Surgical Research, Alfred Hospital & Baker Heart Research Institute, Monash University, Melbourne, Australia

    S. Pepe

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  1. D. Gonsolin
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  2. K. Couturier
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  3. B. Garait
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  10. C. Keriel
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  13. L. Demaison
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Correspondence to L. Demaison.

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Gonsolin, D., Couturier, K., Garait, B. et al. High dietary sucrose triggers hyperinsulinemia, increases myocardial β-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery. Mol Cell Biochem 295, 217–228 (2007). https://doi.org/10.1007/s11010-006-9291-7

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