Journal of Endocrinological Investigation

, Volume 24, Issue 11, pp 838–845 | Cite as

High-fructose diet decreases catalase mRNA levels in rat tissues

  • Alessandro CavarapeEmail author
  • F. Feletto
  • F. Mercuri
  • L. Quagliaro
  • G. Damante
  • A. Ceriello
Original Article


Insulin resistance and hyperinsulinemia have recently been identified as independent determinants of several risk factors for cardiovascular disease. The generation of reactive oxygen species (ROS) may play an important role as a final common mediator by which glucose and insulin resistance might contribute to development of cardiovascular disease and hypertension. The aim of the present study was to evaluate changes on mRNA expression of antioxidant enzymes [catalase, Cu-Zn superoxide dismutase (Cu-ZnSOD), MnSOD], blood pressure and metabolic parameters in insulin resistance that follow feeding normotensive Wistar rats a high-fructose-enriched diet. In our investigation 26 normal male Wistar rats were fed a highfructose diet for 2 weeks (no.=14) or normal chow to serve as a control group (no.=12). In vivo insulin resistance was verified in a subgroup of control and fructose-fed rats by the euglycemic hyperinsulinemic clamp technique at 2 different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol/kg/min respectively. The glucose infusion rate (GIR) was not significantly different in the two groups during the submaximal infusion of insulin (1.4±0.8 mmol/kg/min in fructosefed rats vs 1.6±0.7 mmol/kg/min in control rats, NS) while in fructose-fed rats it was significantly lower (-29.8%) than in control rats during maximal infusion of insulin (2.6±0.3 mmol/kg/min vs 3.7±0.3 mmol/kg/min, p<0.05). Fructose feeding markedly reduced the expression of catalase mRNA and Cu-ZnSOD mRNA in the liver, catalase mRNA in the heart (p<0.05). A tendency of fructose feeding to reduce the expression of antioxidant enzymes in skeletal muscle and adipose tissue was also observed (NS). Fructose feeding also increased plasma uric acid (119.9±30.4 vs 42.1±10 μmol/l, p<0.05) and systemic blood pressure (128±4 vs 109±5 mmHg, p<0.05) respect to control animals. No significant changes were observed in plasma levels of glycemia and tryglycerides. Our study suggests that in non-hyperglycemic, fructose-fed insulin-resistant rats the expression of catalase is inhibited in liver and heart. This condition might lead to higher susceptibility to oxidative stress in insulin resistance. However, an adaptive cellular response to maintain the effectiveness of intracellular signaling pathways mediated by insulinactivated hydrogen peroxide generating systems may also be hypothesized.


High-fructose diet insulin resistance catalase antioxidant enzymes oxidative stress 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Janssen Y.M., Van Houten B., Borm P.J., Mossman B.T. Cell and tissue responses to oxidative damage. Lab. Invest. 1993, 69: 261–274.PubMedGoogle Scholar
  2. 2.
    Mates J.M., Perez-Gomez C., Nunez de Castro I. Antioxidant enzymes and human diseases. Clin. Biochem. 1999, 32: 595–603.PubMedCrossRefGoogle Scholar
  3. 3.
    Harris E.D. Regulation of antioxidant enzymes. FASEB J. 1992, 6: 2675–2683.PubMedGoogle Scholar
  4. 4.
    Darley-Usmar V., Halliwell B. Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm. Res. 1996, 13: 649–662.PubMedCrossRefGoogle Scholar
  5. 5.
    Giugliano D., Ceriello A., Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996, 19: 257–267.PubMedCrossRefGoogle Scholar
  6. 6.
    Ceriello A. Oxidative stress and glycemic regulation. Metabolism 2000, 49(Suppl. 1): 27–29.PubMedCrossRefGoogle Scholar
  7. 7.
    Paolisso G., Giugliano D. Oxidative stress and insulin action: is there a relationship? Diabetologia 1995, 39: 357–363.CrossRefGoogle Scholar
  8. 8.
    Hamaty M., Lamberti M., Sowers J.M. Diabetic vascular disease and hypertension. Curr. Opin. Cardiol. 1998, 13: 298–303.PubMedCrossRefGoogle Scholar
  9. 9.
    Ceriello A., Pirisi M. Is oxidative stress the missing link between insulin resistance and atherosclerosis? Diabetologia 1995, 38: 1484–1485.PubMedCrossRefGoogle Scholar
  10. 10.
    Hwang I.S., Ho H., Hoffman B.B., Reaven G.M. Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987, 10: 512–516.PubMedCrossRefGoogle Scholar
  11. 11.
    Reaven G.M. Insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension: parallels between human disease and rodent models. Diabetes Care 1991, 14: 195–202.PubMedCrossRefGoogle Scholar
  12. 12.
    Lee M.K., Miles P.D., Khoursheed M., Gao K.M., Moossa A.R., Olefsky J.M. Metabolic effects of Troglitazone on fructose-induced insulin resistance in the rat. Diabetes 1994, 43: 1435–1439.PubMedCrossRefGoogle Scholar
  13. 13.
    Chomezinsky P., Sacchi N. A single step method of RNA isolation by acid guanidinium thiocyanate -phenol chloroform extraction. Annal. Biochem. 1987, 162: 157–159.Google Scholar
  14. 14.
    Amstad P., Peskin A., Shah G., Mirault M.E., Moret R., Zbinden I., Cerutti P. The balance between Cu, Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry 1991, 30: 9305–9313.PubMedCrossRefGoogle Scholar
  15. 15.
    Faure P., Rossini E., Lafond J.L., Richard M.J., Favier A., Halimi S. Vitamin E improves the free radical defense system potential and insulin-sensitivity of rats fed with high fructose diets. J. Nutr. 1997, 123: 103–107.Google Scholar
  16. 16.
    Habib M.P., Dickerson F.D., Mooradian A.D. Effect of diabetes, insulin and glucose load on lipid peroxidation in the rat. Metabolism 1994, 43: 1442–1445.PubMedCrossRefGoogle Scholar
  17. 17.
    Paolisso G., D’Amore A., Balbi V., Volpe C., Galzerano C., Giugliano D., Sgambato S., Varricchio M., D’Onofrio F. Plasma vitamin C affects glucose homeostasis in healthy subjects and non-insulin dependent diabetics. Am. J. Physiol. Endocrinol. Metab. 1994, 266: E261–E268.Google Scholar
  18. 18.
    Nolan J.J., Ludvik B., Beerdsen P., Joyce M., Olefski J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N. Engl. J. Med. 1994, 331: 1188–1193.PubMedCrossRefGoogle Scholar
  19. 19.
    Halliwell B., Gutteridge J.M.C. Free radicals in biology and medicine, ed. 2. Clarendon Press, Oxford, 1995.Google Scholar
  20. 20.
    Suzuki Y.J., Forman H.J., Sevanian A. Oxidants as stimulators of signal transduction. Free Radic. Biol. Med. 1997, 22: 269–285.PubMedCrossRefGoogle Scholar
  21. 21.
    Eizirik D.L., Flodstrom M., Karlsen A.E., Welsh N. The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic beta cells. Diabetologia 1996, 39: 875–890.PubMedCrossRefGoogle Scholar
  22. 22.
    Ramasarma T. Generation of H2O2 in biomembranes. Biochim. Biophys. Acta 1982, 694: 69–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Storz G.A., Tartaglia L.A., Ames B.N. Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation. Science 1990, 248: 189–194.PubMedCrossRefGoogle Scholar
  24. 24.
    Malter J.S., Hong Y. A redox switch and phosphorylation are involved in the post-translational up-regulation of the adenosine- uridine binding factor by phorbol ester and ionophore. J. Biol. Chem. 1991, 266: 3167–3171.PubMedGoogle Scholar
  25. 25.
    Krieger-Bauer H.I., Kather H. Human fat cells possess a plasma membrane-bound H2O2-generating system that is activated by insulin via a mechanism bypassing the receptor kinase. J. Clin. Invest. 1992, 89: 1006–1013.CrossRefGoogle Scholar
  26. 26.
    Housley M.D. Crosstalks: a pivotal role for protein kinase C in modulating relationships between signal transduction pathways. Eur. J. Biochem. 1991, 195: 9–27.CrossRefGoogle Scholar
  27. 27.
    Tiedge M., Lortz S., Drinkgern J., Lenzen S. Relation between antioxidant gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997, 46: 1733–1742.PubMedCrossRefGoogle Scholar
  28. 28.
    Michiels C., Raes M., Touissaint O., Remacle J. Importance of Se-glutathione peroxidase, catalase and Cu/Zn SOD for cell survival against oxidative stress. Free Radic. Biol. Med. 1994, 17: 235–248.PubMedCrossRefGoogle Scholar
  29. 29.
    Faure P., Rossini E., Wiernsperger N., Richard M.J., Favier A., Halimi S. An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats. Diabetes 1999, 48: 353–357.PubMedCrossRefGoogle Scholar
  30. 30.
    Fields M., Ferretti R.J., Reiser S., Smith J.C. The severity of copper deficiency in rats is determined by the type of diet carbohydrate. Proc. Soc. Exp. Biol. Med. 1984, 175: 530–537.PubMedCrossRefGoogle Scholar
  31. 31.
    Bray T.M., Bettger W.J. The physiological role of zinc as antioxidant. Free Radic. Res. Med. 1990, 8: 281–291.CrossRefGoogle Scholar
  32. 32.
    Faure P., Roussel A.M., Martini M., Favier A., Halimi S. Insulin-sensitivity in zinc-depleted rats: assessment with the euglycemic hyperinsulinemic clamp technique. Diabetes Metab. 1991, 17: 325–331.Google Scholar
  33. 33.
    Fujii Y., Taniguchi N. Down regulation of superoxide dismutases and glutathione peroxidase by reactive oxygen and nitrogen species. Free Rad. Res. 1999, 31: 301–308CrossRefGoogle Scholar
  34. 34.
    Yamamoto T., Moriwaki Y., Takahashi S., Yamakita J., Tsutsumi Z., Ohata H., Hirohishi K., Nakano T., Higashino K. Effect of ethanol and fructose on plasma uridine and purine bases. Metabolism 1997, 46: 544–547.PubMedCrossRefGoogle Scholar
  35. 35.
    Buemann B., Toubro S., Holst J.J., Rehfeld J.F., Bibby B.M., Astrup A. D-Tagatose, a stereoisomer of D-fructose, increased blood uric acid concentration. Metabolism 2000, 49: 969–976.PubMedCrossRefGoogle Scholar
  36. 36.
    De Fronzo R.A., Ferranini E. Insulin resistance: a multi-faceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14: 173–194.CrossRefGoogle Scholar
  37. 37.
    Wiedmann P., Ferrari P. Central role of sodium in hypertension in diabetic subjects. Diabetes Care 1991, 14: 220–232.CrossRefGoogle Scholar
  38. 38.
    Anderson E.A., Mark A.L. The vasodilator action of insulin: implications for the insulin hypothesis of hypertension. Hypertension 1993, 21: 745–751.Google Scholar
  39. 39.
    Reaven G.M., Lithell H., Landsberg L. Hypertension and associated metabolic abnormalities. The role of insulin resistance and the sympathoadrenal system. N. Engl. J. Med. 1996, 334: 374–381.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2001

Authors and Affiliations

  • Alessandro Cavarape
    • 1
    Email author
  • F. Feletto
    • 1
  • F. Mercuri
    • 2
  • L. Quagliaro
    • 2
  • G. Damante
    • 3
  • A. Ceriello
    • 1
  1. 1.Department of Experimental and Clinical Pathology and Medicine (DPMSC)University of UdineUdineItaly
  2. 2.Morpurgo-Hofman Research Laboratory on AgeingUdineItaly
  3. 3.Department of Science and Biomedical TechnologyUniversity of UdineUdineItaly

Personalised recommendations