{"title":"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。","authors":"Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi","doi":"10.4093/dmj.2025.0106","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":"49 3","pages":"333-347"},"PeriodicalIF":6.8000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086555/pdf/","citationCount":"0","resultStr":"{\"title\":\"Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies.\",\"authors\":\"Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi\",\"doi\":\"10.4093/dmj.2025.0106\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":11153,\"journal\":{\"name\":\"Diabetes & Metabolism Journal\",\"volume\":\"49 3\",\"pages\":\"333-347\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086555/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes & Metabolism Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4093/dmj.2025.0106\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes & Metabolism Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4093/dmj.2025.0106","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.