胰高血糖素样肽-1和下丘脑饱足调节:来自人类和动物研究的认知和神经见解。

IF 6.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi
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引用次数: 0

摘要

胰高血糖素样肽-1受体激动剂(GLP-1RAs)已成为治疗代谢性疾病的重磅药物。胰高血糖素样肽-1 (glucagon -like peptide-1, GLP-1)通过促进胰岛素分泌,抑制胰高血糖素释放,延缓胃排空,并作用于中枢神经系统调节饱腹和饱腹感,在葡萄糖稳态中起关键作用。本文综述了GLP-1的发现和GLP-1RAs的发展,并重点介绍了它们的主要作用机制。人类神经影像学研究表明,GLP-1RAs在食物认知过程中影响大脑活动,支持在摄入前饱腹感中的作用。下丘脑前馈调节饥饿的动物研究表明,认知下丘脑机制也可能有助于饱腹控制。我们强调glp - 1ra诱导饱腹感和饱腹感的脑机制,包括认知影响,重点是下丘脑胰高血糖素样肽-1受体(GLP-1R)和表达GLP-1R的神经元的动物研究。非下丘脑区域的作用也进行了讨论。此外,我们回顾了新兴的联合药物和口服GLP-1RA配方,旨在提高疗效和患者依从性。总之,下丘脑背内侧(DMH)是GLP-1RA的关键靶点,它介导摄入前认知饱足,而下丘脑其他GLP-1R神经元调节摄食行为的各个方面,为肥胖治疗提供了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)-a key GLP-1RA target-mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

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来源期刊
Diabetes & Metabolism Journal
Diabetes & Metabolism Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
10.40
自引率
6.80%
发文量
92
审稿时长
52 weeks
期刊介绍: The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies. The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication. The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.
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