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靶向胃饥饿素通路的治疗潜力。

Therapeutic Potential of Targeting the Ghrelin Pathway.

作者信息

Colldén Gustav, Tschöp Matthias H, Müller Timo D

机构信息

Institute for Diabetes and Obesity & Helmholtz Diabetes Center, Helmholtz Zentrum München German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany.

Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany.

出版信息

Int J Mol Sci. 2017 Apr 11;18(4):798. doi: 10.3390/ijms18040798.

Abstract

Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems' metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

摘要

胃饥饿素于1999年被发现,是生长激素促分泌素受体1a(GHSR1a)的内源性配体。自那时起,人们发现胃饥饿素具有众多生理效应,远远超出了其最初作为生长激素(GH)促分泌素的特征。胃饥饿素众多已明确的效应包括刺激食欲和脂质积累、调节免疫和炎症、刺激胃动力、改善心脏功能、调节应激、焦虑、味觉和奖赏寻求行为,以及调节葡萄糖代谢和产热。由于对系统代谢有多种有益作用,内源性胃饥饿素系统的药物靶向治疗被广泛认为是治疗代谢并发症(如慢性炎症、胃轻瘫或癌症相关厌食和恶病质)的一种有价值的方法。本综述的目的是讨论并强调调节胃饥饿素途径在治疗厌食、恶病质、肌肉减少症、心脏病、神经退行性疾病、肾脏和肺部疾病、胃肠道(GI)疾病、炎症性疾病和代谢综合征方面的广泛药理潜力。

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