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Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates

International Journal of Obesity volume 40, pages 1600–1603 (2016)Cite this article

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Abstract

The inability to augment capillary blood volume (CBV) in response to insulin or glucose is thought to contribute to insulin resistance (IR) by limiting glucose uptake in key storage sites. Understanding the mechanisms that contribute to impaired CBV augmentation early in the onset of IR may lead to new future therapies. We hypothesized that inactivity alters the balance of vasoactive eicosanoids and contributes to microvascular IR. In ten activity-restricted (AR) and six normal activity adult male rhesus macaques, contrast-enhanced ultrasound of skeletal muscle blood flow and CBV was performed at baseline and during intravenous glucose tolerance test (IVGTT). Plasma was analyzed for vasoconstrictor hydroxyeicosatetraenoic acids (HETEs) and the ratio of vasodilatory epoxyeicosatrienoic acids (EETs) to their less biologically active dihydroxyeicosatrienoic acids (DHETs) as an indirect measure of soluble epoxide hydrolase activity. AR primates were IR during IVGTT and had a 45% lower glucose-stimulated CBV response. Vasoconstrictor 18-HETE and 19-HETE and the DHET/EET ratio were markedly elevated in the AR group and correlated inversely with the CBV response. In addition, levels of 18-HETE and 19-HETE correlated directly with microvascular IR. We conclude that a shift toward increased eicosanoid vasoconstrictor tone correlates with abnormal skeletal muscle vascular recruitment and may contribute to IR.

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Acknowledgements

Dr Chadderdon was funded by a Fellow-to-Faculty Award (0875005N) from the American Heart Association and grant 5KL2TR000152 from the National Institutes of Health (NIH). Dr Lindner is supported by grants, R01-HL-078610 and R01-HL-111969 from the NIH. Dr Grove is supported by grant R01-DK-79194 from the NIH. The Oregon National Primate Research Center is supported by a National Center for Research Resources grant (S10-RR-024585) and a Research Program Projects and Centers grant (P51 DK011092) from the NIH. This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Advancing Translational Sciences, a component of the NIH and NIH Roadmap for Medical Research.

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Authors and Affiliations

  1. Knight Cardiovascular Institute,

    S M Chadderdon, J T Belcik & J R Lindner

  2. Oregon Health & Science University, Portland, OR, USA

    S M Chadderdon, J T Belcik & J R Lindner

  3. The Oregon National Primate Research Center,

    L Bader, P Kievit & K L Grove

  4. Oregon Health & Science University, Portland, OR, USA

    L Bader, P Kievit & K L Grove

Authors
  1. S M Chadderdon
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  2. J T Belcik
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  3. L Bader
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  4. P Kievit
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  5. K L Grove
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  6. J R Lindner
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Correspondence to S M Chadderdon.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Chadderdon, S., Belcik, J., Bader, L. et al. Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes 40, 1600–1603 (2016). https://doi.org/10.1038/ijo.2016.117

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