Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.
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Research Article|
September 18 2015
Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity
Lina Zhao;
Lina Zhao
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
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Zhuo Fu;
Zhuo Fu
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
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Jing Wu;
Jing Wu
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
†Department of Endocrinology, Central South University Xiangya Hospital, Changsha, Hunan 410008, China
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Kevin W. Aylor;
Kevin W. Aylor
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
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Eugene J. Barrett;
Eugene J. Barrett
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
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Wenhong Cao;
Wenhong Cao
‡Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27516, U.S.A.
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Zhenqi Liu
*Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.
Correspondence: Dr Zhenqi Liu (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 16 2015
Revision Received:
July 21 2015
Accepted:
August 11 2015
Accepted Manuscript online:
August 12 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (12): 1025–1036.
Article history
Received:
February 16 2015
Revision Received:
July 21 2015
Accepted:
August 11 2015
Accepted Manuscript online:
August 12 2015
Citation
Lina Zhao, Zhuo Fu, Jing Wu, Kevin W. Aylor, Eugene J. Barrett, Wenhong Cao, Zhenqi Liu; Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity. Clin Sci (Lond) 1 December 2015; 129 (12): 1025–1036. doi: https://doi.org/10.1042/CS20150143
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