Regulation of glucose homeostasis by GLP-1.
Regulation of glucose homeostasis by GLP-1.
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DOI：
10.1016/b978-0-12-800101-1.00002-8
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发表时间：
2014
影响因子：
--
通讯作者：
Holz, George G.
中科院分区：
文献类型：
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作者：
Nadkarni, Prashant;Chepurny, Oleg G.;Holz, George G.
胰高血糖素样肽-1(7-36)酰胺 (GLP-1) 是一种分泌肽，具有减缓胃排空、增强胰腺胰岛素分泌和抑制胰腺胰高血糖素分泌的能力，是血糖稳态的关键决定因素。 GLP-1是响应进餐而从胃肠粘膜L细胞分泌的，并且GLP-1的降血糖作用由于其被二肽基肽酶-IV（DPP-IV）的酶促降解而终止。释放的 GLP-1 激活肠道和自主反射，同时还作为肠促胰岛素激素循环，控制内分泌胰腺功能。 GLP-1受体（GLP-1R）是一种G蛋白偶联受体，可被目前用于治疗2型糖尿病（T2DM）的降血糖药物直接或间接激活。这些治疗剂包括GLP-1R激动剂（艾塞那肽、利拉鲁肽、利西拉来、阿必鲁肽、度拉鲁肽和朗格列肽）和DPP-IV抑制剂（西他列汀、维格列汀、沙格列汀、利格列汀和阿格列汀）。用于治疗 T2DM 的研究药物包括刺激 L 细胞释放 GLP-1 的 GPR119 和 GPR40 受体激动剂。这里总结了 GLP-1 在控制血糖稳态中的作用，特别强调了基于 GLP-1 的疗法的优点和局限性。
Glucagon-like peptide-1(7–36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeo-stasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics.