期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 53, 期 5, 页码 1017-1023出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.06.031
关键词
Islet; Insulin secretion; Nitrite; Nitric oxide; Pancreatic islet blood flow
资金
- Stockholm County Council
- Karolinska Institutet
- Swedish Society for Medical Research
- Swedish Society of Medicine
- Swedish Heart and Lung Foundation
- European Foundation for the Study of Diabetes
- Karolinska Institutet's funds
- Ake Wiberg fund
- Vinnova (CIDaT)
- Stiftelsen Berth von Kantzow's
- Stiftelsen Olle Engkvist Byggmastare
Reactive nitrogen and oxygen species have been proposed to be involved in control of insulin release from the pancreatic beta cell. Recent evidence suggests that the supposedly inert anions nitrate and nitrite are metabolized in blood and tissues to form nitric oxide (NO) and other bioactive nitrogen oxides. Here we present evidence for a novel stimulatory role of nitrite in influencing pancreatic islet physiology via a dual mechanism, involving both indirect enhancement (through microcirculation redistribution) and direct insulinotropic effects on the beta cell. In rats, intraperitoneal injection of sodium nitrite increased pancreatic islet blood flow by 50% and serum insulin concentrations by 30%, while whole pancreatic blood flow and glycemia remained unaffected. Nitrite also dose dependently enhanced insulin secretion from rat beta cells in vitro under nonstimulatory glucose concentrations. This effect was not mimicked by nitrate and was abolished by the guanylyl cyclase (GC) inhibitor ODQ and the NO scavenger cPTIO. It was also mimicked by a cyclic GMP agonist (8-CPT-cGMP) and a classical NO donor (NONOate). Interestingly, a reactive oxygen species scavenger (vitamin E analog, Trolox) abolished the insulin secretion induced by nitrite. We conclude that nitrite exerts dual stimulatory effects on pancreatic islet function, including enhancement of islet blood flow and subsequent insulin secretion in vivo and direct stimulation of insulin release in vitro. The insulinotropic effect of nitrite is cGMP-dependent and involves formation of reactive nitrogen and oxygen species. (c) 2012 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据