...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Eating and weight disorders: EWD >GLP-1 receptor independent pathways: emerging beneficial effects of GLP-1 breakdown products
【24h】

GLP-1 receptor independent pathways: emerging beneficial effects of GLP-1 breakdown products

机译：GLP-1受体独立途径：GLP-1击穿产品的新兴效果

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36) amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36) amide, the major circulating form in plasma. GLP-1(28-36) amide and GLP-1(32-36) amide are further cleavage products derived from GLP-1(7-36) amide and GLP-1(9-36) amide by the action of a neutral endopeptidase known as neprilysin. Until recently, GLP-1-derived metabolites were generally considered metabolically inactive. However, emerging evidence indicates that GLP-1 byproducts have insulinomimetic activities that may contribute to the pleiotropic effects of GLP-1 independently of the canonical GLP-1R. The recent studies reporting the beneficial effects of the administration of these metabolites in vivo and in vitro are the focus of this review. Collectively, these results suggest that GLP-1 metabolites inhibit hepatic glucose production, exert antioxidant cardio- and neuroprotective actions, reduce oxidative stress in vasculature and have both antiapoptotic and proliferative effects in pancreatic beta-cells, putatively by the modulation of mitochondrial functions. These findings have implication in energy homeostasis, obesity and its associated metabolic and cardiovascular complications as well as incretin-based therapies for the treatment of diabetes and obesity.
机译：胰高血糖素肽-1（GLP-1）轴作为治疗2型糖尿病的主要治疗靶标，最近是肥胖症的主要治疗靶标。主要通过独特的G蛋白偶联受体（GLP-1R）施加的天然增量素激素GLP-1（7-36）酰胺的胰岛素活性由二肽基肽酶-IV通过酶促切割终止，所述二肽基肽酶-IV产生C. - 终端GLP-1代谢物GLP-1（9-36）酰胺，血浆中的主要循环形式。 GLP-1（28-36）酰胺和GLP-1（32-36）酰胺是通过中性的作用衍生自GLP-1（7-36）酰胺和GLP-1（9-36）酰胺的切割产物内肽酶称为Neprilysin。直到最近，GLP-1衍生的代谢物通常被认为是代谢无活性的。然而，出现的证据表明GLP-1副产品具有胰岛素瘤，可与CANONICAL GLP-1R独立地有助于GLP-1的脂肪效应。最近的研究报告了在体内和体外给予这些代谢物的有益效果是本综述的重点。这些结果表明，GLP-1代谢物抑制肝葡萄糖生产，施加抗氧化体和神经保护作用，降低脉管系统中的氧化应激，并通过调节线粒体功能的调节，在胰腺β细胞中具有抗曝光和增殖作用。这些发现在能量稳态，肥胖症及其相关的代谢和心血管并发症以及基于糖尿病和肥胖症的治疗的疗法中具有含义。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号