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Increased endothelial shear stress improves insulin-stimulated vasodilatation in skeletal muscle.
Walsh, Lauren K; Ghiarone, Thaysa; Olver, T Dylan; Medina-Hernandez, Areli; Edwards, Jenna C; Thorne, Pamela K; Emter, Craig A; Lindner, Jonathan R; Manrique-Acevedo, Camila; Martinez-Lemus, Luis A; Padilla, Jaume.
Afiliação
  • Walsh LK; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
  • Ghiarone T; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
  • Olver TD; Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatchewan, Canada.
  • Medina-Hernandez A; Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
  • Edwards JC; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • Thorne PK; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • Emter CA; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • Lindner JR; Knight Cardiovascular Institute and the Oregon National Primate Research Center, Oregon Health & Science University, Portland, OR, USA.
  • Manrique-Acevedo C; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri, Columbia, MO, USA.
  • Martinez-Lemus LA; Diabetes and Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
  • Padilla J; Research Services, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
J Physiol ; 597(1): 57-69, 2019 01.
Article em En | MEDLINE | ID: mdl-30328623
KEY POINTS: It has been postulated that increased blood flow-associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin-stimulated vasodilatation. This report provides evidence supporting the hypothesis that increased shear stress exerts insulin-sensitizing effects in the vasculature and this evidence is based on experiments in vitro in endothelial cells, ex vivo in isolated arterioles and in vivo in humans. Given the recognition that vascular insulin signalling, and associated enhanced microvascular perfusion, contributes to glycaemic control and maintenance of vascular health, strategies that stimulate an increase in limb blood flow and shear stress have the potential to have profound metabolic and vascular benefits mediated by improvements in endothelial insulin sensitivity. ABSTRACT: The vasodilator actions of insulin contribute to glucose uptake by skeletal muscle, and previous studies have demonstrated that acute and chronic physical activity improves insulin-stimulated vasodilatation and glucose uptake. Because this effect of exercise primarily manifests in vascular beds highly perfused during exercise, it has been postulated that increased blood flow-associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin-stimulated vasodilatation. Accordingly, herein we tested the hypothesis that increased shear stress, in the absence of muscle contraction, can acutely render the vascular endothelium more insulin-responsive. To test this hypothesis, complementary experiments were conducted using (1) cultured endothelial cells, (2) isolated and pressurized skeletal muscle arterioles from swine, and (3) humans. In cultured endothelial cells, 1 h of increased shear stress from 3 to 20 dynes cm-2 caused a significant shift in insulin signalling characterized by greater activation of eNOS relative to MAPK. Similarly, isolated arterioles exposed to 1 h of intraluminal shear stress (20 dynes cm-2 ) subsequently exhibited greater insulin-induced vasodilatation compared to arterioles kept under no-flow conditions. Finally, we found in humans that increased leg blood flow induced by unilateral limb heating for 1 h subsequently augmented insulin-stimulated popliteal artery blood flow and muscle perfusion. In aggregate, these findings across models (cells, isolated arterioles and humans) support the hypothesis that elevated shear stress causes the vascular endothelium to become more insulin-responsive and thus are consistent with the notion that shear stress may be a principal mechanism by which physical activity enhances insulin-stimulated vasodilatation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arteríolas / Estresse Mecânico / Endotélio Vascular / Músculo Esquelético / Células Endoteliais / Insulina Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arteríolas / Estresse Mecânico / Endotélio Vascular / Músculo Esquelético / Células Endoteliais / Insulina Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article