Skip to main content
SpringerLink
Log in

The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The metabolic syndrome is an important public health concern that predisposes individuals to the development of cardiovascular disease and/or Type 2 diabetes. The fructose-fed rat is an animal model of acquired systolic hypertension that displays numerous features of the metabolic syndrome. This animal model is used to study the relationship between insulin resistance/compensatory hyperinsulinemia and the development of hypertension. Several mechanisms have been proposed to mediate the link between insulin resistance and hypertension. In this review, we have addressed the role of sympathetic nervous system overactivation, increased production of vasoconstrictors, such as endothelin-1 and angiotensin II, and prostanoids in the development of hypertension in fructose-fed rats. The roles of nitric oxide, impaired endothelium-dependent relaxation and sex hormones in the pathogenesis of the fructose-fed induced hypertensive rats have also been highlighted. More recently, increased formation of reactive oxygen species and elevated levels of uric acid have been reported to contribute to fructose-induced hypertension.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607

    Article  PubMed  CAS  Google Scholar 

  2. Wajchenberg BL, Malerbi DA, Rocha MS, Lerario AC, Santomauro AT (1994) Syndrome X: a syndrome of insulin resistance. Epidemiological and clinical evidence. Diabetes Metab Rev 10:19–29

    Article  PubMed  CAS  Google Scholar 

  3. Hanson RL, Imperatore G, Bennett PH, Knowler WC (2002) Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 51:3120–3127

    Article  PubMed  CAS  Google Scholar 

  4. Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA (2002) Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 156:1070–1077

    Article  PubMed  Google Scholar 

  5. Lorenzo C, Okoloise M, Williams K, Stern MP, Haffner SM (2003) The metabolic syndrome as predictor of type 2 diabetes: the San Antonio heart study. Diabetes Care 26:3153–3159

    Article  PubMed  Google Scholar 

  6. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689

    Article  PubMed  CAS  Google Scholar 

  7. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716

    Article  PubMed  Google Scholar 

  8. Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR (2004) Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 110:1245–1250

    Article  PubMed  Google Scholar 

  9. Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP (2004) National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 110:1251–1257

    Article  PubMed  Google Scholar 

  10. Ginsberg HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest 106:453–458

    Article  PubMed  CAS  Google Scholar 

  11. DeFronzo RA (1992) Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. J Cardiovasc Pharmacol 20(Suppl 11):S1–S16

    Article  PubMed  Google Scholar 

  12. Bhanot S, McNeill JH (1996) Insulin and hypertension: a causal relationship? Cardiovasc Res 31:212–221

    PubMed  CAS  Google Scholar 

  13. DeFronzo RA, Ferrannini E (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173–194

    Article  PubMed  CAS  Google Scholar 

  14. Reaven GM (1991) Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension. Am J Med 90:7S–12S

    Article  PubMed  CAS  Google Scholar 

  15. Verma S, McNeill JH (2000) Insulin resistance and hypertension: pharmacological and mechanistic studies. Can J Diabetes Care 23(Suppl 2):23–42

    Google Scholar 

  16. Reaven GM (1991) Relationship between insulin resistance and hypertension. Diabetes Care 14(Suppl 4):33–38

    PubMed  Google Scholar 

  17. Grunfeld B, Balzareti M, Romo M, Gimenez M, Gutman R (1994) Hyperinsulinemia in normotensive offspring of hypertensive parents. Hypertension 23:I12–I15

    PubMed  CAS  Google Scholar 

  18. Mondon CE, Reaven GM (1988) Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension. Metabolism 37:303–305

    Article  PubMed  CAS  Google Scholar 

  19. Hulman S, Falkner B, Chen YQ (1991) Insulin resistance in the spontaneously hypertensive rat. Metabolism 40:359–361

    Article  PubMed  CAS  Google Scholar 

  20. Bhanot S, Michoulas A, McNeill JH (1995) Antihypertensive effects of vanadium compounds in hyperinsulinemic, hypertensive rats. Mol Cell Biochem 153:205–209

    Article  PubMed  CAS  Google Scholar 

  21. Kotchen TA, Zhang HY, Covelli M, Blehschmidt N (1991) Insulin resistance and blood pressure in Dahl rats and in one-kidney, one-clip hypertensive rats. Am J Physiol 261:E692–E697

    PubMed  CAS  Google Scholar 

  22. Somova L, Channa ML (1999) Glucose metabolism and insulin sensitivity in Dahl hypertensive rats. Methods Find Exp Clin Pharmacol 21:421–425

    Article  PubMed  CAS  Google Scholar 

  23. Hwang IS, Ho H, Hoffman BB, Reaven GM (1987) Fructose-induced insulin resistance and hypertension in rats. Hypertension 10:512–516

    PubMed  CAS  Google Scholar 

  24. Dall’Aglio E, Tosini P, Zavaroni I, Olivetti G, Reaven GM (1995) Comparison of the metabolic changes in rats with hypertension secondary to fructose feeding or renal artery stenosis. Am J Hypertens 8:524–527

    Article  PubMed  Google Scholar 

  25. Yuen VG, Pederson RA, Dai S, Orvig C, McNeill JH (1996) Effects of low and high dose administration of bis(maltolato)oxovanadium(IV) on fa/fa Zucker rats. CJPP 74(9):1001–1009

    CAS  Google Scholar 

  26. Alonso-Galicia M, Brands MW, Zappe DH, Hall JE (1996) Hypertension in obese Zucker rats. Role of antiotensin II and adrenergic activity. Hypertension 28:1047–1054

    PubMed  CAS  Google Scholar 

  27. Lesniewski LA, Donato AJ, Behnke BJ, Woodmand CR, Laughlin MH, Ray CA, Delp MD (2008) Decreased NO signaling leads to enhanced vasocaonstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension. AJPP 294(4):H1840–H1850

    CAS  Google Scholar 

  28. Imai G, Satoh T, Kumai T, Murao M, Tsuchida H, Shima Y, Ogimot G, Fujino T, Kobayashi S, Kimura K (2003) Hypertension accelerates diabetic nephropathy in Wistar fatty rats, a model of type 2 diabetes mellitus, via mitogen-activated protein kinase cascades and transforming growth factor-beta 1. Hypertens Res 26:339–347

    Article  PubMed  CAS  Google Scholar 

  29. Rutledge AC, Adeli K (2007) Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms. Nutr Rev 65:S13–S23

    Article  PubMed  Google Scholar 

  30. Havel PJ (2005) Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63:133–157

    Article  PubMed  Google Scholar 

  31. Mayes PA (1993) Intermediary metabolism of fructose. Am J Clin Nutr 58:754S–765S

    PubMed  CAS  Google Scholar 

  32. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76(5):911–922

    PubMed  CAS  Google Scholar 

  33. Daly ME, Vale C, Walker M, Alberti KG, Mathers JC (1997) Dietary carbohydrates and insulin sensitivity: a review of the evidence and clinical implications. Am J Clin Nutr 66:1072–1085

    PubMed  CAS  Google Scholar 

  34. Parks EJ, Hellerstein MK (2000) Carbohydrate-induced hypertriacylglycerolemia: a historical perspective and review of biological mechanisms. Am J Clin Nutr 71(2):412–433

    PubMed  CAS  Google Scholar 

  35. Swanson JE, Laine DC, Thomas W, Bantle JP (1992) Metabolic effects of dietary fructose in healthy subjects. Am J Clin Nutr 55(4):851–856

    PubMed  CAS  Google Scholar 

  36. Vasdev S, Longerich L, Gill V (2004) Prevention of fructose-induced hypertension by dietary vitamins. Clin Biochem 37(1):1–9

    Article  PubMed  CAS  Google Scholar 

  37. Curry DL (1989) Effects of mannose and fructose on the synthesis and secretion of insulin. Pancreas 4:2–9

    Article  PubMed  CAS  Google Scholar 

  38. Ganda OP, Soeldner JS, Gleason RE, Cleator IG, Reynolds C (1979) Metabolic effects of glucose, mannose, galactose, and fructose in man. J Clin Endocrinol Metab 49:616–622

    Article  PubMed  CAS  Google Scholar 

  39. Rayner CK, Park HS, Wishart JM, Kong M, Doran SM, Horowitz M (2000) Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans. Am J Physiol Regul Integr Comp Physiol 278:R360–R366

    PubMed  CAS  Google Scholar 

  40. Teff KL, Elliott SS, Tschop M, Kieffer TJ, Rader D, Heiman M, Townsend RR, Keim NL, D’Alessio D, Havel PJ (2004) Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 89:2963–2972

    Article  PubMed  CAS  Google Scholar 

  41. Adams SH, Stanhope KL, Grant RW, Cummings BP, Havel PJ (2008) Metabolic and endocrine profiles in response to systemic infusion of fructose and glucose in rhesus macaques. Endocrinology 149:3002–3008

    Article  PubMed  CAS  Google Scholar 

  42. Roglans N, Vila L, Farre M, Alegret M, Sanchez RM, Vazquez-Carrera M, Laguna JC (2007) Impairment of hepatic Stat-3 activation and reduction of PPARalpha activity in fructose-fed rats. Hepatology 45:778–788

    Article  PubMed  CAS  Google Scholar 

  43. Lee YC, Ko YH, Hsu YP, Ho LT (2006) Plasma leptin response to oral glucose tolerance and fasting/re-feeding tests in rats with fructose-induced metabolic derangements. Life Sci 78:1155–1162

    Article  PubMed  CAS  Google Scholar 

  44. Kamari Y, Grossman E, Oron-Herman M, Peleg E, Shabtay Z, Shamiss A, Sharabi Y (2007) Metabolic stress with a high carbohydrate diet increases adiponectin levels. Horm Metab Res 39:384–388

    Article  PubMed  CAS  Google Scholar 

  45. Verma S, Bhanot S, McNeill JH (1994) Antihypertensive effects of metformin in fructose-fed hyperinsulinemic, hypertensive rats. J Pharmacol Exp Ther 271:1334–1337

    PubMed  CAS  Google Scholar 

  46. Galipeau D, Arikawa E, Sekirov I, McNeill JH (2001) Chronic thromboxane synthase inhibition prevents fructose-induced hypertension. Hypertension 38:872–876

    PubMed  CAS  Google Scholar 

  47. Iyer SN, Katovich MJ (1994) Effect of chronic losartan potassium treatment on fructose-induced hypertension. Life Sci 55:PL139–PL144

    Article  PubMed  CAS  Google Scholar 

  48. Iyer SN, Katovich MJ (1996) Vascular reactivity to phenylephrine and angiotensin II in hypertensive rats associated with insulin resistance. Clin Exp Hypertens 18:227–242

    Article  PubMed  CAS  Google Scholar 

  49. Juan CC, Fang VS, Hsu YP, Huang YJ, Hsia DB, Yu PC, Kwok CF, Ho LT (1998) Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model. J Hypertens 16:1775–1782

    Article  PubMed  CAS  Google Scholar 

  50. Hsieh PS, Tai YH, Loh CH, Shih KC, Cheng WT, Chu CH (2005) Functional interaction of AT1 and AT2 receptors in fructose-induced insulin resistance and hypertension in rats. Metabolism 54:157–164

    Article  PubMed  CAS  Google Scholar 

  51. Brands MW, Garrity CA, Holman MG, Keen HL, Alonso-Galicia M, Hall JE (1994) High-fructose diet does not raise 24-hour mean arterial pressure in rats. Am J Hypertens 7:104–109

    PubMed  CAS  Google Scholar 

  52. D’Angelo G, Elmarakby AA, Pollock DM, Stepp DW (2005) Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats. Hypertension 46:806–811

    Article  PubMed  Google Scholar 

  53. Dai S, McNeill JH (1995) Fructose-induced hypertension in rats is concentration- and duration-dependent. J Pharmacol Toxicol Methods 33:101–107

    Article  PubMed  CAS  Google Scholar 

  54. Takagawa Y, Berger ME, Hori MT, Tuck ML, Golub MS (2001) Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries. Am J Hypertens 14:811–817

    Article  PubMed  CAS  Google Scholar 

  55. Park SK, Meyer TW (1992) The effects of fructose feeding on glomerular structure in the rat. J Am Soc Nephrol 3:1330–1332

    PubMed  CAS  Google Scholar 

  56. Tobey TA, Mondon CE, Zavaroni I, Reaven GM (1982) Mechanism of insulin resistance in fructose-fed rats. Metabolism 31:608–612

    Article  PubMed  CAS  Google Scholar 

  57. Thorburn AW, Storlien LH, Jenkins AB, Khouri S, Kraegen EW (1989) Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. Am J Clin Nutr 49:1155–1163

    PubMed  CAS  Google Scholar 

  58. Baret G, Peyronnet J, Grassi-Kassisse D, Dalmaz Y, Wiernsperger N, Geloen A (2002) Increased intraabdominal adipose tissue mass in fructose fed rats: correction by metformin. Exp Clin Endocrinol Diabetes 110:298–303

    Article  PubMed  CAS  Google Scholar 

  59. Higashiura K, Ura N, Takada T, Li Y, Torii T, Togashi N, Takada M, Takizawa H, Shimamoto K (2000) The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats. Am J Hypertens 13:290–297

    Article  PubMed  CAS  Google Scholar 

  60. Galipeau D, Verma S, McNeill JH (2002) Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol 283:H2478–H2484

    PubMed  CAS  Google Scholar 

  61. Song D, Arikawa E, Galipeau D, Battell M, McNeill JH (2004) Androgens are necessary for the development of fructose-induced hypertension. Hypertension 43:667–672

    Article  PubMed  CAS  Google Scholar 

  62. Tay A, Ozcelikay AT, Altan VM (2002) Effects of l-arginine on blood pressure and metabolic changes in fructose-hypertensive rats. Am J Hypertens 15:72–77

    Article  PubMed  CAS  Google Scholar 

  63. Navarro-Cid J, Maeso R, Perez-Vizcaino F, Cachofeiro V, Ruilope LM, Tamargo J, Lahera V (1995) Effects of losartan on blood pressure, metabolic alterations, and vascular reactivity in the fructose-induced hypertensive rat. Hypertension 26:1074–1078

    PubMed  CAS  Google Scholar 

  64. Navarro-Cid J, Maeso R, Perez-Vizcaino F, Casal MC, Cachofeiro V, Ruilope LM, Tamargo J, Lahera V (1996) Effects of antihypertensive drugs on blood pressure and metabolic alterations in the fructose-induced hypertensive rat. Am J Hypertens 9:669–674

    Article  PubMed  CAS  Google Scholar 

  65. Behr-Roussel D, Oudot A, Caisey S, Coz OL, Gorny D, Bernabe J, Wayman C, Alexandre L, Giuliano FA (2008) Daily treatment with sildenafil reverses endothelial dysfunction and oxidative stress in an animal model of insulin resistance. Eur Urol 53:1272–1281

    Article  PubMed  CAS  Google Scholar 

  66. Iyer SN, Katovich MJ (1996) Effect of acute and chronic losartan treatment on glucose tolerance and insulin sensitivity in fructose-fed rats. Am J Hypertens 9:662–668

    Article  PubMed  CAS  Google Scholar 

  67. Miatello R, Risler N, Gonzalez S, Castro C, Ruttler M, Cruzado M (2002) Effects of enalapril on the vascular wall in an experimental model of syndrome X. Am J Hypertens 15:872–878

    Article  PubMed  CAS  Google Scholar 

  68. Chen S, Noguchi Y, Izumida T, Tatebe J, Katayama S (1996) A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone. J Hypertens 14:1325–1330

    Article  PubMed  CAS  Google Scholar 

  69. Iimura O, Shimamoto K, Matsuda K, Masuda A, Takizawa H, Higashiura K, Miyazaki Y, Hirata A, Ura N, Nakagawa M (1995) Effects of angiotensin receptor antagonist and angiotensin converting enzyme inhibitor on insulin sensitivity in fructose-fed hypertensive rats and essential hypertensives. Am J Hypertens 8:353–357

    Article  PubMed  CAS  Google Scholar 

  70. Catena C, Giacchetti G, Novello M, Colussi G, Cavarape A, Sechi LA (2003) Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension. Am J Hypertens 16:973–978

    Article  PubMed  CAS  Google Scholar 

  71. Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ (2000) A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J Nutr 130:1531–1535

    PubMed  CAS  Google Scholar 

  72. Deutsch DD, Jen KL, Grunberger G (1993) Regulation of hepatic insulin receptor tyrosine kinase in rat models of mild insulin resistance. J Lab Clin Med 122:421–425

    PubMed  CAS  Google Scholar 

  73. Reaven GM, Ho H, Hoffman BB (1988) Attenuation of fructose-induced hypertension in rats by exercise training. Hypertension 12:129–132

    PubMed  CAS  Google Scholar 

  74. Reaven GM, Ho H, Hoffmann BB (1989) Somatostatin inhibition of fructose-induced hypertension. Hypertension 14:117–120

    PubMed  CAS  Google Scholar 

  75. Verma S, Yao L, Dumont AS, McNeill JH (2000) Metformin treatment corrects vascular insulin resistance in hypertension. J Hypertens 18:1445–1450

    Article  PubMed  CAS  Google Scholar 

  76. Bhanot S, McNeill JH, Bryer-Ash M (1994) Vanadyl sulfate prevents fructose-induced hyperinsulinemia and hypertension in rats. Hypertension 23:308–312

    PubMed  CAS  Google Scholar 

  77. Lee MK, Miles PD, Khoursheed M, Gao KM, Moossa AR, Olefsky JM (1994) Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat. Diabetes 43:1435–1439

    Article  PubMed  CAS  Google Scholar 

  78. Kotchen TA, Reddy S, Zhang HY (1997) Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat. Am J Hypertens 10:1020–1026

    Article  PubMed  CAS  Google Scholar 

  79. Miller AW, Hoenig ME, Ujhelyi MR (1998) Mechanisms of impaired endothelial function associated with insulin resistance. J Cardiovasc Pharmacol Ther 3:125–134

    Article  PubMed  CAS  Google Scholar 

  80. Verma S, Bhanot S, Yao L, McNeill JH (1996) Defective endothelium-dependent relaxation in fructose-hypertensive rats. Am J Hypertens 9:370–376

    Article  PubMed  CAS  Google Scholar 

  81. Katakam PV, Ujhelyi MR, Hoenig ME, Miller AW (1998) Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am J Physiol 275:R788–R792

    PubMed  CAS  Google Scholar 

  82. Miller AW, Katakam PV, Ujhelyi MR (1999) Impaired endothelium-mediated relaxation in coronary arteries from insulin-resistant rats. J Vasc Res 36:385–392

    Article  PubMed  CAS  Google Scholar 

  83. Vasudevan H, Nagareddy PR, McNeill JH (2006) Gonadectomy prevents endothelial dysfunction in fructose-fed male rats, a factor contributing to the development of hypertension. Am J Physiol Heart Circ Physiol 291:H3058–H3064

    Article  PubMed  CAS  Google Scholar 

  84. Katakam PV, Ujhelyi MR, Miller AW (1999) EDHF-mediated relaxation is impaired in fructose-fed rats. J Cardiovasc Pharmacol 34:461–467

    Article  PubMed  CAS  Google Scholar 

  85. Kamata K, Yamashita K (1999) Insulin resistance and impaired endothelium-dependent renal vasodilatation in fructose-fed hypertensive rats. Res Commun Mol Pathol Pharmacol 103:195–210

    PubMed  CAS  Google Scholar 

  86. Verma S, Skarsgard P, Bhanot S, Yao L, Laher I, McNeill JH (1997) Reactivity of mesenteric arteries from fructose hypertensive rats to endothelin-1. Am J Hypertens 10:1010–1019

    Article  PubMed  CAS  Google Scholar 

  87. Shinozaki K, Ayajiki K, Nishio Y, Sugaya T, Kashiwagi A, Okamura T (2004) Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance. Hypertension 43:255–262

    Article  PubMed  CAS  Google Scholar 

  88. Si X, Webb RC, Richey JM (1999) Bezafibrate, an anti-hypertriglyceridemic drug, attenuates vascular hyperresponsiveness and elevated blood pressure in fructose-induced hypertensive rats. Can J Physiol Pharmacol 77:755–762

    Article  PubMed  CAS  Google Scholar 

  89. Bunnag P, Hori MT, Ormsby B, Berger ME, Golub MS, Tuck ML (1997) Impaired in vivo adrenergic responses in diet-induced hypertensive rats. Hypertens Res 20:17–21

    Article  PubMed  CAS  Google Scholar 

  90. Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P (1994) Nitric oxide release accounts for insulin’s vascular effects in humans. J Clin Invest 94:2511–2515

    Article  PubMed  CAS  Google Scholar 

  91. Zeng G, Quon MJ (1996) Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest 98:894–898

    Article  PubMed  CAS  Google Scholar 

  92. Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS (1997) Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes 46(Suppl 2):S9–S13

    PubMed  CAS  Google Scholar 

  93. Panza JA, Quyyumi AA, Callahan TS, Epstein SE (1993) Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. J Am Coll Cardiol 21:1145–1151

    Article  PubMed  CAS  Google Scholar 

  94. Rosen P, Ohly P, Gleichmann H (1997) Experimental benefit of moxonidine on glucose metabolism and insulin secretion in the fructose-fed rat. J Hypertens Suppl 15:S31–S38

    PubMed  CAS  Google Scholar 

  95. Penicaud L, Berthault MF, Morin J, Dubar M, Ktorza A, Ferre P (1998) Rilmenidine normalizes fructose-induced insulin resistance and hypertension in rats. J Hypertens Suppl 16:S45–S49

    Article  PubMed  CAS  Google Scholar 

  96. Verma S, Bhanot S, McNeill JH (1999) Sympathectomy prevents fructose-induced hyperinsulinemia and hypertension. Eur J Pharmacol 373:R1–R4

    Article  PubMed  CAS  Google Scholar 

  97. Verma S, Bhanot S, McNeill JH (1995) Effect of chronic endothelin blockade in hyperinsulinemic hypertensive rats. Am J Physiol 269:H2017–H2021

    PubMed  CAS  Google Scholar 

  98. Cosenzi A, Bernobich E, Plazzotta N, Seculin P, Bellini G (1999) Bosentan reduces blood pressure and the target-organ damage induced by a high-fructose diet in rats. J Hypertens 17:1843–1848

    Article  PubMed  CAS  Google Scholar 

  99. Kobayashi R, Nagano M, Nakamura F, Higaki J, Fujioka Y, Ikegami H, Mikami H, Kawaguchi N, Onishi S, Ogihara T (1993) Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats. Hypertension 21:1051–1055

    PubMed  CAS  Google Scholar 

  100. Rattigan S, Clark MG, Barrett EJ (1999) Acute vasoconstriction-induced insulin resistance in rat muscle in vivo. Diabetes 48:564–569

    Article  PubMed  CAS  Google Scholar 

  101. Mayer MA, Hocht C, Opezzo JA, Peredo HA, Navacchia D, Taira CA, Fernandez BE, Puyo AM (2006) Role of hypothalamic alpha-adrenoceptor activity in fructose-induced hypertension. Clin Exp Pharmacol Physiol 33:904–909

    Article  PubMed  CAS  Google Scholar 

  102. Kamide K, Rakugi H, Higaki J, Okamura A, Nagai M, Moriguchi K, Ohishi M, Satoh N, Tuck ML, Ogihara T (2002) The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats. Am J Hypertens 15:66–71

    Article  PubMed  CAS  Google Scholar 

  103. Hsieh PS, Huang WC (2001) Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats. Chin J Physiol 44:25–31

    PubMed  CAS  Google Scholar 

  104. Hogikyan RV, Supiano MA (1994) Arterial alpha-adrenergic responsiveness is decreased and SNS activity is increased in older humans. Am J Physiol 266:E717–E724

    PubMed  CAS  Google Scholar 

  105. Sun CL, Hanig JP (1983) Vascular reactivity to adrenergic agents and neuronal and vascular catecholamine levels in spontaneously hypertensive rats. Pharmacology 27:319–324

    Article  PubMed  CAS  Google Scholar 

  106. Takagawa Y, Berger ME, Tuck ML, Golub MS (2002) Impaired endothelial alpha-2 adrenergic receptor-mediated vascular relaxation in the fructose-fed rat. Hypertens Res 25:197–202

    Article  PubMed  CAS  Google Scholar 

  107. Perez del Villar C, Garcia Alonso CJ, Feldstein CA, Juncos LA, Romero JC (2005) Role of endothelin in the pathogenesis of hypertension. Mayo Clin Proc 80:84–96

    Article  PubMed  Google Scholar 

  108. Oliver FJ, de la Rubia G, Feener EP, Lee ME, Loeken MR, Shiba T, Quertermous T, King GL (1991) Stimulation of endothelin-1 gene expression by insulin in endothelial cells. J Biol Chem 266:23251–23256

    PubMed  CAS  Google Scholar 

  109. Frank HJ, Levin ER, Hu RM, Pedram A (1993) Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells. Endocrinology 133:1092–1097

    Article  PubMed  CAS  Google Scholar 

  110. Wolpert HA, Steen SN, Istfan NW, Simonson DC (1993) Insulin modulates circulating endothelin-1 levels in humans. Metabolism 42:1027–1030

    Article  PubMed  CAS  Google Scholar 

  111. Juan CC, Shen YW, Chien Y, Lin YJ, Chang SF, Ho LT (2004) Insulin infusion induces endothelin-1-dependent hypertension in rats. Am J Physiol Endocrinol Metab 287:E948–E954

    Article  PubMed  CAS  Google Scholar 

  112. Nguyen PV, Parent A, Deng LY, Fluckiger JP, Thibault G, Schiffrin EL (1992) Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats. Hypertension 19:II98–II104

    PubMed  CAS  Google Scholar 

  113. Lee DH, Lee JU, Kang DG, Paek YW, Chung DJ, Chung MY (2001) Increased vascular endothelin-1 gene expression with unaltered nitric oxide synthase levels in fructose-induced hypertensive rats. Metabolism 50:74–78

    Article  PubMed  CAS  Google Scholar 

  114. Zhao C, Wang P, Xiao X, Chao J, Chao L, Wang DW, Zeldin DC (2003) Gene therapy with human tissue kallikrein reduces hypertension and hyperinsulinemia in fructose-induced hypertensive rats. Hypertension 42:1026–1033

    Article  PubMed  CAS  Google Scholar 

  115. Kang DG, Moon MK, Sohn EJ, Lee DH, Lee HS (2004) Effects of morin on blood pressure and metabolic changes in fructose-induced hypertensive rats. Biol Pharm Bull 27:1779–1783

    Article  PubMed  CAS  Google Scholar 

  116. Yu JC, Davenport AP (1995) Regulation of endothelin receptor expression in vascular smooth-muscle cells. J Cardiovasc Pharmacol 26(Suppl 3):S348–S350

    PubMed  CAS  Google Scholar 

  117. Katakam PV, Pollock JS, Pollock DM, Ujhelyi MR, Miller AW (2001) Enhanced endothelin-1 response and receptor expression in small mesenteric arteries of insulin-resistant rats. Am J Physiol Heart Circ Physiol 280:H522–H527

    PubMed  CAS  Google Scholar 

  118. Jiang J, Tran L, Vasudevan H, Xia Z, Yuen VG, McNeill JH (2007) Endothelin-1 blockade prevents COX2 induction and TXA2 production in the fructose hypertensive rat. Can J Physiol Pharmacol 85:422–429

    Article  PubMed  CAS  Google Scholar 

  119. Cosenzi A, Bernobich E, Bonavita M, Bertola G, Trevisan R, Bellini G (2002) Antihypertensive treatment with enrasentan (SB217242) in an animal model of hypertension and hyperinsulinemia. J Cardiovasc Pharmacol 39:488–495

    Article  PubMed  CAS  Google Scholar 

  120. Ezra-Nimni O, Ezra D, Peleg E, Munter K, Rosenthal T (2003) Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat. Am J Hypertens 16:324–328

    Article  PubMed  CAS  Google Scholar 

  121. Tran LT, Macleod KM and McNeill JH (2009) Endothelin-1 modulates angiotensin II in the development of hypertension in fructose-fed rats. Mol Cell Biochem 325(1–2):89–97

    Google Scholar 

  122. Diep QN, El Mabrouk M, Cohn JS, Endemann D, Amiri F, Virdis A, Neves MF, Schiffrin EL (2002) Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma. Circulation 105:2296–2302

    Article  PubMed  CAS  Google Scholar 

  123. Rao RH (1994) Effects of angiotensin II on insulin sensitivity and fasting glucose metabolism in rats. Am J Hypertens 7:655–660

    PubMed  CAS  Google Scholar 

  124. Hwang IS, Huang WC, Wu JN, Shian LR, Reaven GM (1989) Effect of fructose-induced hypertension on the renin-angiotensin-aldosterone system and atrial natriuretic factor. Am J Hypertens 2:424–427

    PubMed  CAS  Google Scholar 

  125. Iyer SN, Katovich MJ, Raizada MK (1996) Changes in angiotensin AT1 receptor density during hypertension in fructose-fed rats. Adv Exp Med Biol 396:49–58

    PubMed  CAS  Google Scholar 

  126. Iyer SN, Raizada MK, Katovich MJ (1996) AT1 receptor density changes during development of hypertension in hyperinsulinemic rats. Clin Exp Hypertens 18:793–810

    Article  PubMed  CAS  Google Scholar 

  127. Nyby MD, Abedi K, Smutko V, Eslami P, Tuck ML (2007) Vascular Angiotensin type 1 receptor expression is associated with vascular dysfunction, oxidative stress and inflammation in fructose-fed rats. Hypertens Res 30:451–457

    Article  PubMed  CAS  Google Scholar 

  128. Giacchetti G, Sechi LA, Griffin CA, Don BR, Mantero F, Schambelan M (2000) The tissue renin-angiotensin system in rats with fructose-induced hypertension: overexpression of type 1 angiotensin II receptor in adipose tissue. J Hypertens 18:695–702

    Article  PubMed  CAS  Google Scholar 

  129. Uchida T, Okumura K, Ito T, Kamiya H, Nishimoto Y, Yamada M, Tomida T, Matsui H, Hayakawa T (2002) Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats. Clin Exp Pharmacol Physiol 29:381–385

    Article  PubMed  CAS  Google Scholar 

  130. Erlich Y, Rosenthal T (1995) Effect of angiotensin-converting enzyme inhibitors on fructose induced hypertension and hyperinsulinaemia in rats. Clin Exp Pharmacol Physiol Suppl 22:S347–S349

    Article  PubMed  CAS  Google Scholar 

  131. Wiemer G, Scholkens BA, Becker RH, Busse R (1991) Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 18:558–563

    PubMed  CAS  Google Scholar 

  132. Campbell DJ, Kladis A, Valentijn AJ (1995) Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol 26:233–240

    Article  PubMed  CAS  Google Scholar 

  133. Miatello R, Risler N, Castro C, Cruzado M, Gonzalez S, Zumino AP (2003) Chronic administration of losartan reverses cardiovascular changes in hypertensive fructose-fed rats. Cell Mol Biol (Noisy-le-grand) 49:945–952

    CAS  Google Scholar 

  134. Sellers MM, Stallone JN (2008) Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure. Am J Physiol Heart Circ Physiol 294:H1978–H1986

    Article  PubMed  CAS  Google Scholar 

  135. Yanagisawa-Miwa A, Ito H, Sugimoto T (1990) Effects of insulin on vasoconstriction induced by thromboxane A2 in porcine coronary artery. Circulation 81:1654–1659

    PubMed  CAS  Google Scholar 

  136. Behr-Roussel D, Oudot A, Compagnie S, Gorny D, Le Coz O, Bernabe J, Wayman C, Alexandre L, Giuliano F (2008) Impact of a long-term sildenafil treatment on pressor response in conscious rats with insulin resistance and hypertriglyceridemia. Am J Hypertens 21:1258–1263

    Article  PubMed  CAS  Google Scholar 

  137. Hsieh PS, Tsai HC, Kuo CH, Chan JY, Shyu JF, Cheng WT, Liu TT (2008) Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose-fed rats. Eur J Clin Invest 38:812–819

    Article  PubMed  CAS  Google Scholar 

  138. Richey JM, Si X, Halter JB, Webb RC (1998) Fructose perfusion in rat mesenteric arteries impairs endothelium-dependent vasodilation. Life Sci 62:PL55–PL62

    Article  PubMed  CAS  Google Scholar 

  139. Puyo AM, Mayer MA, Cavallero S, Donoso AS, Peredo HA (2004) Fructose overload modifies vascular morphology and prostaglandin production in rats. Auton Autacoid Pharmacol 24:29–35

    Article  PubMed  CAS  Google Scholar 

  140. Peredo HA, Mayer MA, Rodriguez Fermepin M, Grinspon D, Puyo AM (2006) Oral treatment and in vitro incubation with fructose modify vascular prostanoid production in the rat. Auton Autacoid Pharmacol 26:15–20

    Article  PubMed  CAS  Google Scholar 

  141. De Meyer GR, Herman AG (1997) Vascular endothelial dysfunction. Prog Cardiovasc Dis 39:325–342

    Article  PubMed  Google Scholar 

  142. Schiffrin EL (1994) The endothelium and control of blood vessel function in health and disease. Clin Invest Med 17:602–620

    PubMed  CAS  Google Scholar 

  143. Rees DD, Palmer RM, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A 86:3375–3378

    Article  PubMed  CAS  Google Scholar 

  144. Lockette W, Otsuka Y, Carretero O (1986) The loss of endothelium-dependent vascular relaxation in hypertension. Hypertension 8:II61–II66

    PubMed  CAS  Google Scholar 

  145. Luscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 8:344–348

    PubMed  CAS  Google Scholar 

  146. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27

    Article  PubMed  CAS  Google Scholar 

  147. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87:1468–1474

    PubMed  CAS  Google Scholar 

  148. Endemann DH, Schiffrin EL (2004) Endothelial dysfunction. J Am Soc Nephrol 15:1983–1992

    Article  PubMed  CAS  Google Scholar 

  149. Verma S, Bhanot S, Yao L, McNeill JH (1997) Vascular insulin resistance in fructose-hypertensive rats. Eur J Pharmacol 322:R1–R2

    Article  PubMed  CAS  Google Scholar 

  150. Shinozaki K, Kashiwagi A, Nishio Y, Okamura T, Yoshida Y, Masada M, Toda N, Kikkawa R (1999) Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2-imbalance in insulin-resistant rat aorta. Diabetes 48:2437–2445

    Article  PubMed  CAS  Google Scholar 

  151. Shinozaki K, Nishio Y, Okamura T, Yoshida Y, Maegawa H, Kojima H, Masada M, Toda N, Kikkawa R, Kashiwagi A (2000) Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats. Circ Res 87:566–573

    PubMed  CAS  Google Scholar 

  152. Galipeau DM, Yao L, McNeill JH (2002) Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex. Am J Physiol Heart Circ Physiol 283:H562–H567

    PubMed  CAS  Google Scholar 

  153. Song D, Arikawa E, Galipeau DM, Yeh JN, Battell ML, Yuen VG, McNeill JH (2005) Chronic estrogen treatment modifies insulin-induced insulin resistance and hypertension in ovariectomized rats. Am J Hypertens 18:1189–1194

    Article  PubMed  CAS  Google Scholar 

  154. Vasudevan H, Xiang H, McNeill JH (2005) Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Am J Physiol Heart Circ Physiol 289:H1335–H1342

    Article  PubMed  CAS  Google Scholar 

  155. Janssen YM, Van Houten B, Borm PJ, Mossman BT (1993) Cell and tissue responses to oxidative damage. Lab Invest 69:261–274

    PubMed  CAS  Google Scholar 

  156. Eriksson JW (2007) Metabolic stress in insulin’s target cells leads to ROS accumulation—a hypothetical common pathway causing insulin resistance. FEBS Lett 581:3734–3742

    Article  PubMed  CAS  Google Scholar 

  157. de Champlain J, Wu R, Girouard H, Karas M, El Midaoui A, Laplante MA, Wu L (2004) Oxidative stress in hypertension. Clin Exp Hypertens 26:593–601

    Article  PubMed  CAS  Google Scholar 

  158. Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Halimi S (1997) Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets. J Nutr 127:103–107

    PubMed  CAS  Google Scholar 

  159. Faure P, Rossini E, Wiernsperger N, Richard MJ, Favier A, Halimi S (1999) An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes 48:353–357

    Article  PubMed  CAS  Google Scholar 

  160. Delbosc S, Paizanis E, Magous R, Araiz C, Dimo T, Cristol JP, Cros G, Azay J (2005) Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 179:43–49

    Article  PubMed  CAS  Google Scholar 

  161. Polizio AH, Gonzales S, Munoz MC, Pena C, Tomaro ML (2006) Behaviour of the anti-oxidant defence system and heme oxygenase-1 protein expression in fructose-hypertensive rats. Clin Exp Pharmacol Physiol 33:734–739

    PubMed  CAS  Google Scholar 

  162. Kashiwagi A, Shinozaki K, Nishio Y, Okamura T, Toda N, Kikkawa R (1999) Free radical production in endothelial cells as a pathogenetic factor for vascular dysfunction in the insulin resistance state. Diabetes Res Clin Pract 45:199–203

    Article  PubMed  CAS  Google Scholar 

  163. Cavarape A, Feletto F, Mercuri F, Quagliaro L, Daman G, Ceriello A (2001) High-fructose diet decreases catalase mRNA levels in rat tissues. J Endocrinol Invest 24:838–845

    PubMed  CAS  Google Scholar 

  164. Song D, Hutchings S, Pang CC (2005) Chronic N-acetylcysteine prevents fructose-induced insulin resistance and hypertension in rats. Eur J Pharmacol 508:205–210

    Article  PubMed  CAS  Google Scholar 

  165. Al-Awwadi NA, Bornet A, Azay J, Araiz C, Delbosc S, Cristol JP, Linck N, Cros G, Teissedre PL (2004) Red wine polyphenols alone or in association with ethanol prevent hypertension, cardiac hypertrophy, and production of reactive oxygen species in the insulin-resistant fructose-fed rat. J Agric Food Chem 52:5593–5597

    Article  PubMed  CAS  Google Scholar 

  166. Hallfrisch J (1990) Metabolic effects of dietary fructose. FASEB J 4:2652–2660

    PubMed  CAS  Google Scholar 

  167. Nakagawa T, Tuttle KR, Short RA, Johnson RJ (2005) Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 1:80–86

    Article  PubMed  CAS  Google Scholar 

  168. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106

    Article  PubMed  CAS  Google Scholar 

  169. Sanchez-Lozada LG, Tapia E, Jimenez A, Bautista P, Cristobal M, Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ, Herrera-Acosta J, Franco M (2007) Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Renal Physiol 292:F423–F429

    Article  PubMed  CAS  Google Scholar 

  170. Sanchez-Lozada LG, Tapia E, Bautista-Garcia P, Soto V, Avila-Casado C, Vega-Campos IP, Nakagawa T, Zhao L, Franco M, Johnson RJ (2008) Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 294:F710–F718

    Article  PubMed  CAS  Google Scholar 

  171. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006) A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 290:F625–F631

    Article  PubMed  CAS  Google Scholar 

  172. Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W, Krotova K, Block ER, Prabhakar S, Johnson RJ (2005) Hyperuricemia induces endothelial dysfunction. Kidney Int 67:1739–1742

    Article  PubMed  Google Scholar 

  173. Kang DH, Park SK, Lee IK, Johnson RJ (2005) Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol 16:3553–3562

    Article  PubMed  CAS  Google Scholar 

  174. Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Loffler MG, Cresswell J, Yu XX, Murray SF, Bhanot S, Monia BP, Bogan JS, Samuel V, Shulman GI (2009) The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance. Cell Metab 9:252–264

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Studies conducted from our laboratory were supported by the Heart and Stroke Foundation of British Columbia & Yukon and the Canadian Institute for Health Research. LTT was the recipient of a Graduate Research Scholarship in Pharmacy from the Health Research Foundation of Canada’s Research-Based Pharmaceutical Companies and the Canadian Institute for Health Research, a Pacific Century Graduate Scholarship from the University of British Columbia and a program grant from the Canadian Institute for Health Research. The authors thank Dr. V. Sharma for constructive comments in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Division of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada

    Linda T. Tran, Violet G. Yuen & John H. McNeill

Authors
  1. Linda T. Tran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Violet G. Yuen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John H. McNeill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John H. McNeill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tran, L.T., Yuen, V.G. & McNeill, J.H. The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 332, 145–159 (2009). https://doi.org/10.1007/s11010-009-0184-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0184-4

Keywords

Search

Navigation