GLP-1R in diabetes mellitus: from basic discovery to therapeutics development
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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1610512/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184173375979520 |
|---|---|
| author | Shujun Li Nanqu Huang Nanqu Huang Mei Wang Wendi Huang Yong Luo Yong Luo Yong Luo Juan Huang |
| author_facet | Shujun Li Nanqu Huang Nanqu Huang Mei Wang Wendi Huang Yong Luo Yong Luo Yong Luo Juan Huang |
| author_sort | Shujun Li |
| collection | DOAJ |
| description | 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 α, β and δ 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 β-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 α-cells, β-cells and δ-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. |
| format | Article |
| id | doaj-art-e22e34b8f98949a39c15b9435929b693 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e22e34b8f98949a39c15b9435929b6932025-08-20T02:17:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.16105121610512GLP-1R in diabetes mellitus: from basic discovery to therapeutics developmentShujun Li0Nanqu Huang1Nanqu Huang2Mei Wang3Wendi Huang4Yong Luo5Yong Luo6Yong Luo7Juan Huang8Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaNational Drug Clinical Trial Institution, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaDepartment of Geriatrics, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaDepartment of Geriatrics, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaDepartment of Neurology, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou, ChinaChinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi, Guizhou, ChinaKey Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaDiabetes 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 α, β and δ 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 β-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 α-cells, β-cells and δ-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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1610512/fullglucagon-like peptide-1 receptordiabetes mellitusβ-cellinsulin secretionblood glucose |
| spellingShingle | Shujun Li Nanqu Huang Nanqu Huang Mei Wang Wendi Huang Yong Luo Yong Luo Yong Luo Juan Huang GLP-1R in diabetes mellitus: from basic discovery to therapeutics development Frontiers in Pharmacology glucagon-like peptide-1 receptor diabetes mellitus β-cell insulin secretion blood glucose |
| title | GLP-1R in diabetes mellitus: from basic discovery to therapeutics development |
| title_full | GLP-1R in diabetes mellitus: from basic discovery to therapeutics development |
| title_fullStr | GLP-1R in diabetes mellitus: from basic discovery to therapeutics development |
| title_full_unstemmed | GLP-1R in diabetes mellitus: from basic discovery to therapeutics development |
| title_short | GLP-1R in diabetes mellitus: from basic discovery to therapeutics development |
| title_sort | glp 1r in diabetes mellitus from basic discovery to therapeutics development |
| topic | glucagon-like peptide-1 receptor diabetes mellitus β-cell insulin secretion blood glucose |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1610512/full |
| work_keys_str_mv | AT shujunli glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT nanquhuang glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT nanquhuang glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT meiwang glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT wendihuang glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT yongluo glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT yongluo glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT yongluo glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment AT juanhuang glp1rindiabetesmellitusfrombasicdiscoverytotherapeuticsdevelopment |