【摘要】 胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)是肠道L细胞分泌的一种由30个氨基酸组成的多肽,具有促进胰岛素分泌,抑制胰高血糖素分泌和刺激胰岛β细胞增殖等生物学作用。GLP-1在体内主要以GLP-1(7-36a)的形式存在。GLP-1(7-36a)的半衰期很短(1～2 min),可被二肽基肽酶4(diaminopeptidyl peptidase-4,DPP4)迅速降解为GLP-1(9-36a),因此GLP-1(9-36a)是GLP-1在循环中的主要存在形式。GLP-1不仅具有调控血糖和能量代谢的作用,还有保护心肌细胞、改善心脏功能和舒张血管等作用,直接或间接发挥心血管保护效应。心血管疾病是2型糖尿病的常见并发症和首要死因。目前基于GLP-1的2型糖尿病药物研发主要有两个方向:可以抵抗DPP4降解的GLP-1受体(GLP-1R)激动剂和DPP4抑制剂。虽然,这两种方法均可延长内源性GLP-1的作用,但显然未兼顾GLP-1(9-36a)对心脏的保护效应。本文通过总结GLP-1(7-36a)及GLP-1(9-36a)在心血管效应方面的异同及其生理学研究进展,探讨GLP-1应用于心血管疾病治疗的新策略。更多还原

【Abstract】 Glucagon-like peptide-1(GLP-1)is a 30-amino acid peptide hormone produced by intestinal L cells in response to food consumption.GLP-1(7-37)or GLP-1 amide(7-36 a)exerts insulinotropic effects including stimulating insulin secretion,suppressing glucagon release and promoting pancreaticβ-cell proliferation.The half-life of native 7-36 a is very short(1-2 min)due to the degrading emzyme diaminopeptidyl peptidase-4(DPP4)that cleaves 7-36 a at position 2 alanine to form GLP-1(9-36 a),which is the major circulating form.In addition to its glucose and energy regulatory effects,7-36 a and its metabolites 9-36 a have direct cardiovascular effects,including preserving cardiomyocyte viability and improving cardiac function.Cardiovascular disease is a common co-morbidity and leading cause of death in type 2 diabetes mellitus.Currently,there are two GLP-1 based therapies:development of DPP4-resistant GLP-1 receptor(GLP-1 R)agonists and DPP4 inhibitors.The two therapeutic strategies are all aimed at prolonging endogenous GLP-1 actions,while,lack of the cardiovascular benefits induced by 9-36 a.This work reviewed the advance in GLP-1 biology and attempted to distinguish the cardiovascular effects between7-36 a and9-36 a,aiming to provide new insights for the development of new strategy for GLP-1 therapies for the treatment of cardiovascular diseases.更多还原