胰高血糖素
胰高血糖素受体
内科学
内分泌学
胰高血糖素样肽-1
胰岛素
胰高血糖素样肽1受体
受体
医学
肠促胰岛素
利拉鲁肽
糖尿病
2型糖尿病
化学
胰高血糖素样肽-2
葡萄糖稳态
作者
Chengsheng Han,Yulin Zhang,Wenzhen Zhu,Guoyi Yang,Xiaohong Peng,Sohum Mehta,Jin Zhang,Yanmei Liu,Liangyi Chen
出处
期刊:Social Science Research Network
[Social Science Electronic Publishing]
日期:2018-01-01
摘要
Despite the well-known role of the GLP-1 receptor (GLP-1R) in potentiating glucose-stimulated insulin secretion (GSIS) and as a therapeutic drug target in diabetes treatment, how GLP-1R is activated under physiological and pathological conditions remains elusive. Against preconceptions in the field, we prove that glucagon released from pancreatic α-cells serves as the principal ligand for GLP-1R on β-cells and is essential for GSIS in normal mice. Activation of the cognate glucagon receptor (GCGR) by glucagon amplifies GSIS evoked by intermediate concentrations of glucose only, as high glucose bypasses GCGR in increasing cytosolic cAMP from the same downstream pool. As the endogenous dual-receptor agonist, glucagon switches from GLP-1R to GCGR in β-cells of mice fed a high-fat diet, which significantly enhances GSIS and reduces body weight. Therefore, developing dual-receptor agonists that target balanced activation of GCGR and GLP-1R in vivo may better preserve glycemic control than the activation of GLP-1R alone.
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