Acute Nitric Oxide Synthase Inhibition Accelerates Transendothelial Insulin Efflux In Vivo

Diabetes
Ian M WilliamsDavid H Wasserman

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...Continue Reading

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Citations

Sep 19, 2019·American Journal of Physiology. Endocrinology and Metabolism·P Mason McClatcheyDavid H Wasserman
Sep 4, 2019·Clinical and Experimental Pharmacology & Physiology·Cathryn M Kolka
Jul 1, 2020·F1000Research·Ann Louise Olson, Kenneth Humphries
Feb 19, 2020·American Journal of Physiology. Endocrinology and Metabolism·P Mason McClatcheyChristopher G Ellis

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