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

Scott Chadderdon, J. T. Belcik, L. Bader, Paul Kievit, Kevin Grove, Jonathan Lindner

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4 Citations (Scopus)

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.International Journal of Obesity advance online publication, 26 July 2016; doi:10.1038/ijo.2016.117.

Original languageEnglish (US)
JournalInternational Journal of Obesity
DOIs
StateAccepted/In press - Jul 26 2016

Fingerprint

Eicosanoids
Vasoconstrictor Agents
Primates
Insulin Resistance
Blood Volume
Insulin
Hydroxyeicosatetraenoic Acids
Glucose Tolerance Test
Glucose
Skeletal Muscle
Epoxide Hydrolases
Acids
Macaca mulatta
Blood Vessels
Publications
Obesity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates",
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.International Journal of Obesity advance online publication, 26 July 2016; doi:10.1038/ijo.2016.117.",
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AU - Chadderdon, Scott

AU - Belcik, J. T.

AU - Bader, L.

AU - Kievit, Paul

AU - Grove, Kevin

AU - Lindner, Jonathan

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