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1 Medicine/Cardiovascular Diease, University of Alabama at Birmingham, birmingham, Alabama, United States
2 pharmacology, University of New England, College of Osteopathic Medicine, Biddeford, Maine, United States
* To whom correspondence should be addressed. E-mail: jchatham{at}uab.edu.
Increased levels of O-linked attachment of N-acetyl-glucosamine (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, resulted in defects in cardiomyocyte mechanical function and if so whether this was 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 to age-matched lean controls. Cardiomyocytes isolated from 22-week old hyperglycemic ZDF rats exhibited significantly impaired relaxation, compared to both age-matched lean controls and 6-week old ZDF groups. There was also a significant increase in O-GlcNAc levels in high-molecular weight proteins in 22-week old ZDF group compared to age-matched lean controls and 6-week 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-weeks 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.
This article has been cited by other articles:
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  S. A. Marsh, L. J. Dell'Italia, and J. C. Chatham Interaction of diet and diabetes on cardiovascular function in rats Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H282 - H292. [Abstract] [Full Text] [PDF]
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