Pandey Sudhir, Mangmool Supachoke, Parichatikanond Warisara
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Pharmaceuticals (Basel). 2023 Jun 3;16(6):836. doi: 10.3390/ph16060836.
Diabetes is one of the chronic metabolic disorders which poses a multitude of life-debilitating challenges, including cardiac muscle impairment, which eventually results in heart failure. The incretin hormone glucagon-like peptide-1 (GLP-1) has gained distinct recognition in reinstating glucose homeostasis in diabetes, while it is now largely accepted that it has an array of biological effects in the body. Several lines of evidence have revealed that GLP-1 and its analogs possess cardioprotective effects by various mechanisms related to cardiac contractility, myocardial glucose uptake, cardiac oxidative stress and ischemia/reperfusion injury, and mitochondrial homeostasis. Upon binding to GLP-1 receptor (GLP-1R), GLP-1 and its analogs exert their effects via adenylyl cyclase-mediated cAMP elevation and subsequent activation of cAMP-dependent protein kinase(s) which stimulates the insulin release in conjunction with enhanced Ca and ATP levels. Recent findings have suggested additional downstream molecular pathways stirred by long-term exposure of GLP-1 analogs, which pave the way for the development of potential therapeutic molecules with longer lasting beneficial effects against diabetic cardiomyopathies. This review provides a comprehensive overview of the recent advances in the understanding of the GLP-1R-dependent and -independent actions of GLP-1 and its analogs in the protection against cardiomyopathies.
糖尿病是一种慢性代谢紊乱疾病，它带来了众多使人衰弱的挑战，包括心肌损伤，最终导致心力衰竭。肠促胰岛素激素胰高血糖素样肽-1（GLP-1）在恢复糖尿病患者的葡萄糖稳态方面已获得显著认可，而目前人们普遍认为它在体内具有一系列生物学效应。多项证据表明，GLP-1及其类似物通过与心脏收缩力、心肌葡萄糖摄取、心脏氧化应激和缺血/再灌注损伤以及线粒体稳态相关的多种机制具有心脏保护作用。GLP-1及其类似物与GLP-1受体（GLP-1R）结合后，通过腺苷酸环化酶介导的环磷酸腺苷（cAMP）升高以及随后激活cAMP依赖性蛋白激酶发挥作用，这些激酶在增强钙和三磷酸腺苷（ATP）水平的同时刺激胰岛素释放。最近的研究结果表明，长期暴露于GLP-1类似物会引发额外的下游分子途径，这为开发对糖尿病性心肌病具有更持久有益作用的潜在治疗分子铺平了道路。本综述全面概述了在理解GLP-1及其类似物在预防心肌病方面依赖GLP-1R和不依赖GLP-1R的作用方面的最新进展。
