HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Davidoff, A. J. Articles by Ren, J. Search for Related Content PubMed PubMed Citation Articles by Davidoff, A. J. Articles by Ren, J.

Sucrose-induced cardiomyocyte dysfunction is both preventable and reversible with clinically relevant treatments

¹Department of Pharmacology, College of Osteopathic Medicine, University of New England, Biddeford, Maine 04005; ²Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203; and ³Division of Pharmaceutical Sciences, University of Wyoming College of Health Sciences, Laramie, Wyoming 82071

Submitted 7 August 2003 ; accepted in final form 2 January 2004

We recently identified cardiomyocyte dysfunction in the early stage of type 2 diabetes (i.e., diet-induced insulin resistance). The present investigation was designed to determine whether a variety of clinically relevant interventions are sufficient to prevent and reverse cardiomyocyte dysfunction in sucrose (SU)-fed insulin-resistant rats. Subsets of animals were allowed to exercise (free access to wheel attached to cage) or were treated with bezafibrate in drinking water to determine whether these interventions would prevent the adverse effects of SU feeding on cardiomyocyte function. After 6–8 wk on diet and treatment, animals were surgically prepared to assess whole body insulin sensitivity (intravenous glucose tolerance test), and isolated ventricular myocyte mechanics were evaluated (video edge recording). SU feeding produced hyperinsulinemia and hypertriglyceridemia, with euglycemia, and induced characteristic whole body insulin resistance. Both exercise and bezafibrate treatment prevented these metabolic abnormalities. Ventricular myocyte shortening and relengthening were slower in SU-fed rats (42–63%) compared with starch (ST)-fed controls, and exercise or bezafibrate completely prevented cardiomyocyte dysfunction in SU-fed rats. In separate cohorts of animals, after 5 wk of SU feeding, animals were either switched back to an ST diet or given menhaden oil for an additional 7–9 wk to determine whether the cardiomyocyte dysfunction was reversible. Both interventions have previously been shown to have favorable metabolic effects, and both improved myocyte mechanics, but only the ST diet reversed all indications of cardiomyocyte dysfunction induced by SU feeding. Thus phenotypic changes in cardiomyocyte mechanics associated with early stages of type 2 diabetes were found to be both preventable and reversible with clinically relevant treatments, suggesting that the cellular processes contributing to this dysfunction are modifiable.

type 2 diabetes; fish oil; exercise; fibrates

This article has been cited by other articles:

				R. M. Witteles and M. B. Fowler Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options J. Am. Coll. Cardiol., January 15, 2008; 51(2): 93 - 102. [Abstract] [Full Text] [PDF]

				R. Loganathan, M. Bilgen, B. Al-Hafez, S. V. Zhero, M. D. Alenezy, and I. V. Smirnova Exercise training improves cardiac performance in diabetes: in vivo demonstration with quantitative cine-MRI analyses J Appl Physiol, February 1, 2007; 102(2): 665 - 672. [Abstract] [Full Text] [PDF]

				Z. Vasanji, E. J. F. Cantor, D. Juric, M. Moyen, and T. Netticadan Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance Am J Physiol Cell Physiol, October 1, 2006; 291(4): C772 - C780. [Abstract] [Full Text] [PDF]