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Journal of Diabetes Research
Volume 2015 (2015), Article ID 153829, 9 pages
http://dx.doi.org/10.1155/2015/153829
Research Article

Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

1Discipline of Biotechnology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia
2Discipline of Surgery, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia
3Discipline of Haematology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia
4Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA
5Discipline of Human Physiology, School of Medicine, Flinders University, Bedford Park, SA 5042, Australia

Received 6 May 2015; Revised 20 July 2015; Accepted 26 July 2015

Academic Editor: Raffaele Marfella

Copyright © 2015 Samira Tajbakhsh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1 per se are not sufficient to prematurely shorten vascular telomeres.