Oxyntomodulin physiology and its therapeutic development in obesity and associated complications.

IF 4.7 2区 医学 Q1 NEUROSCIENCES Journal of Physiology-London Pub Date : 2024-11-04 DOI:10.1113/JP287407
Martin T W Kueh, Ming Chuen Chong, Alexander D Miras, Carel W le Roux
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Abstract

Incretins, such as glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving 'health gains' goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges. This review will discuss the physiological actions of OXM, primarily appetite regulation, energy expenditure, and glucose homeostasis. Finally, we will shed light on the development of OXM-based therapies for obesity and associated complications, and outline important considerations for more translational efforts.

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Oxyntomodulin 的生理学及其在肥胖症和相关并发症中的治疗发展。
胰高血糖素样肽-1(GLP1)和葡萄糖依赖性促胰岛素多肽(GIP)等内分泌素将肥胖症的治疗推向了一个新的高峰。与单一的增量素效应不同,oxyntomodulin(OXM)可激活胰高血糖素受体(GCGR)和胰高血糖素样肽-1受体(GLP1R),显示出更多动态效应,更有可能符合肥胖症治疗中不断发展的 "健康收益 "目标。在此,我们将回顾从其诞生到最近的发展和挑战的分子见解。本综述将讨论 OXM 的生理作用,主要是食欲调节、能量消耗和葡萄糖稳态。最后,我们将阐明基于 OXM 的肥胖症及相关并发症疗法的发展,并概述更多转化工作的重要考虑因素。
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来源期刊
Journal of Physiology-London
Journal of Physiology-London 医学-神经科学
CiteScore
9.70
自引率
7.30%
发文量
817
审稿时长
2 months
期刊介绍: The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew. The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.
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