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Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats

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Abstract

Background

Fructose consumption produces deleterious metabolic effects in animal models. The sites of fructose-induced insulin resistance are documented to be the liver, skeletal muscle, and adipose tissue, but effects of fructose-rich diet on cardiac insulin signaling and action were not investigated.

Purpose and methods

In order to study the potential fructose effects on development of cardiac insulin resistance, we analyzed biochemical parameters relevant for insulin action and phosphorylation of insulin signaling molecules, plasma membrane glucose transporter type 4 (GLUT4) content, and phosphorylation of endothelial nitric oxide synthase (eNOS), in ovariectomized female rats on fructose-enriched diet, in basal and insulin-stimulated conditions.

Results

Fructose-fed rats (FFR) had increased content of visceral adipose tissue, but not body weight. Food intake was decreased, while fluid and caloric intake were increased in FFR. Additionally, fructose diet increased plasma insulin, blood triglycerides level, and HOMA index. Stimulation of protein kinase B (Akt) signaling pathway by insulin was reduced in rats on fructose-enriched diet, but effect of fructose on extracellular signal-regulated kinase (Erk 1/2) phosphorylation was not observed. Furthermore, insulin-induced GLUT4 presence in plasma membranes of cardiac cells was decreased by fructose diet, as well as insulin stimulation of eNOS phosphorylation at Ser1177.

Conclusion

In summary, these results strongly support our hypothesis that fructose diet-induced changes of plasma lipid profile and insulin sensitivity are accompanied with decrease in cardiac insulin action in ovariectomized female rats.

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Acknowledgments

This study was supported by the Project grant No. 41009 and No. 173033 (to E.R.I.) from the Ministry of Science and Technological Development, Republic of Serbia.

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Authors and Affiliations

  1. Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001, Belgrade, Serbia

    Zorica Zakula, Goran Koricanac, Snezana Tepavcevic, Mojca Stojiljkovic & Tijana Milosavljevic

  2. Laboratory of Radiobiology and Molecular Genetics, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia

    Esma R. Isenovic

Authors
  1. Zorica Zakula
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  2. Goran Koricanac
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  3. Snezana Tepavcevic
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  4. Mojca Stojiljkovic
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  5. Tijana Milosavljevic
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  6. Esma R. Isenovic
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Correspondence to Zorica Zakula.

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Zakula, Z., Koricanac, G., Tepavcevic, S. et al. Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats. Eur J Nutr 50, 543–551 (2011). https://doi.org/10.1007/s00394-010-0161-4

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  • DOI: https://doi.org/10.1007/s00394-010-0161-4

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