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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/C1370    most recent 00422.2006v1 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 ISI 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 ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Fülöp, N. Articles by Chatham, J. C. Search for Related Content PubMed PubMed Citation Articles by Fülöp, N. Articles by Chatham, J. C.

CELLULAR METABOLISM

Impact of Type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart

¹Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; ²Department of Pharmacology, College of Osteopathic Medicine, University of New England, Biddeford, Maine; and ³Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 7 August 2006 ; accepted in final form 26 November 2006

Increased levels of O-linked attachment of N-acetylglucosamine (O-GlcNAc) on nucleocytoplasmic proteins are implicated in the development of diabetic cardiomyopathy and are regulated by O-GlcNAc transferase (OGT) expression and its substrate UDP-GlcNAc. Therefore, the goal of this study was to determine whether the development of diabetes in the Zucker diabetic fatty (ZDF) rat, a model of Type 2 diabetes, results in defects in cardiomyocyte mechanical function and, if so, whether this is associated with increased levels of O-GlcNAc and increased OGT expression. Six-week-old ZDF rats were hyperinsulinemic but normoglycemic, and there were no differences in cardiomyocyte mechanical function, UDP-GlcNAc, O-GlcNAc, or OGT compared with age-matched lean control rats. Cardiomyocytes isolated from 22-wk-old hyperglycemic ZDF rats exhibited significantly impaired relaxation, compared with both age-matched lean control and 6-wk-old ZDF groups. There was also a significant increase in O-GlcNAc levels in high-molecular-mass proteins in the 22-wk-old ZDF group compared with age-matched lean control and 6-wk-old ZDF groups; this was associated with increased UDP-GlcNAc levels but not increased OGT expression. Surprisingly, there was a significant decrease in overall O-GlcNAc levels between 6 and 22 wk of age in lean, ZDF, and Sprague-Dawley rats that was associated with decreased OGT expression. These results support the notion that an increase in O-GlcNAc on specific proteins may contribute to impaired cardiomyocyte function in diabetes. However, this study also indicates that in the heart the level of O-GlcNAc on proteins appears to be differentially regulated by age and diabetes.

hexosamine biosynthesis; protein O-glycosylation; O-linked N-acetylglucosamine transferase

This article has been cited by other articles:

				P. H. McNulty Hexosamine biosynthetic pathway flux and cardiomyopathy in type 2 diabetes mellitus. Focus on "Impact of type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart" Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1243 - C1244. [Full Text] [PDF]