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.