{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:54:19Z","timestamp":1787756059292,"version":"build-2784847793"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Diabetes mellitus (DM), a metabolic disorder syndrome characterized by persistent hyperglycemia, has a complex pathogenesis. As the number of diabetic patients continues to grow globally, this disease has become a major and growing challenge in global public health. Glucagon-like peptide-1 receptor (GLP-1R) is a G protein-coupled receptor widely expressed on the surface of a wide range of cells in the human body, including pancreatic islet \u03b1, \u03b2 and \u03b4 cells, as well as multiple tissues such as the intestines, stomach, lungs, heart, kidneys, and central nervous system. GLP-1R works through the combination of the endogenous ligand Glucagon-like peptide-1 (GLP-1) or exogenous agonists, which activate multiple intracellular signaling pathways that enhance insulin secretion, inhibit glucagon secretion, protect \u03b2-cells from apoptosis, delay gastric emptying and increase satiety. This makes GLP-1R a key target for diabetes treatment. This paper reviews the structural and functional characteristics of GLP-1R. Its role in glucose homeostasis and its application in diabetes treatment. It focuses on the mechanism of action of GLP-1R in pancreatic islet \u03b1-cells, \u03b2-cells and \u03b4-cells, as well as its effects on the central nervous system and gastrointestinal tract. In addition, the article reviews the clinical progress of GLP-1R agonists, including their efficacy, safety and potential in the treatment of diabetes and related complications.<\/jats:p>","DOI":"10.3389\/fphar.2025.1610512","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:43:10Z","timestamp":1748583790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["GLP-1R in diabetes mellitus: from basic discovery to therapeutics development"],"prefix":"10.3389","volume":"16","author":[{"given":"Shujun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanqu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"736","DOI":"10.3390\/ph17060736","article-title":"Potential role of phytochemicals as glucagon-like peptide 1 receptor (GLP-1R) agonists in the treatment of diabetes mellitus","volume":"17","author":"Abiola","year":"2024","journal-title":"Pharm. 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