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Publication
Acute Nitric Oxide Synthase Inhibition Accelerates Transendothelial Insulin
Efflux In Vivo.
Authors Williams IM, McClatchey PM, Bracy DP, Valenzuela FA, Wasserman DH
Submitted By Submitted Externally on 11/5/2018
Status Published
Journal Diabetes
Year 2018
Date Published 10/1/2018
Volume : Pages 67 : 1962 - 1975
PubMed Reference 30002132
Abstract Before insulin can stimulate glucose uptake in muscle, it must be delivered to
skeletal muscle (SkM) through the microvasculature. Insulin delivery is
determined by SkM perfusion and the rate of movement of insulin across the
capillary endothelium. The endothelium therefore plays a central role in
regulating insulin access to SkM. Nitric oxide (NO) is a key regulator of
endothelial function and stimulates arterial vasodilation, which increases SkM
perfusion and the capillary surface area available for insulin exchange. The
effects of NO on transendothelial insulin efflux (TIE), however, are unknown. We
hypothesized that acute reduction of endothelial NO would reduce TIE. However,
intravital imaging of TIE in mice revealed that reduction of NO by
l-NG-nitro-l-arginine methyl ester (l-NAME) enhanced the rate of TIE by ~30% and
increased total extravascular insulin delivery. This accelerated TIE was
associated with more rapid insulin-stimulated glucose lowering. Sodium
nitroprusside, an NO donor, had no effect on TIE in mice. The effects of l-NAME
on TIE were not due to changes in blood pressure alone, as a direct-acting
vasoconstrictor (phenylephrine) did not affect TIE. These results demonstrate
that acute NO synthase inhibition increases the permeability of capillaries to
insulin, leading to an increase in delivery of insulin to SkM.




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