ArticleNature metabolism2023
Functional screening and rational design of compounds targeting GPR132 to treat diabetes.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Article
- GPR132 antagonists alleviate atherosclerosis by suppressing M1 polarization and subsequent VSMCs proliferation and migration as revealed by transcriptomic profiling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXII. Applying an objective evaluation to the status of class A orphan G protein-coupled receptors.Pharmacological reviews · 2026Review
- First Structure-Activity-Relationship Study of Potent G2A Antagonists.Journal of medicinal chemistry · 2026Article
- Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.Journal of translational medicine · 2026Review
- Inhibition of the cancer stem cell immune checkpoint SOAT1 suppresses regulatory T cell functions through a trans-cellular 20(S)-Hydroxycholesterol-GPR132 pathway in mice.Nature communications · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Constitutive activity among orphan G protein-coupled receptors: Molecular mechanisms and pharmacological perspectives.Molecular pharmacology · 2026Review
- Progress on Omega-3 fatty acids for the comprehensive and targeted treatment of spinal cord injury.Bone research · 2026Review
- Subspace Method of Moments forSIAM journal on imaging sciences · 2026Article
- Effect of Xiaonang Yusi decoction () on IVF outcomes in patients with phlegm-dampness type PCOS: a prospective cohort study with supporting metabolomics, network pharmacology, and molecular docking analysis.Frontiers in medicine · 2026Article
- The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery.Metabolism open · 2025Review
- Lactate-Activated GPR132-Src Signal Induces Macrophage Senescence and Aggravates Atherosclerosis Under Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- The regulatory functions of G protein-coupled receptors signaling pathways in B cell differentiation and development contributing to autoimmune diseases.Cell & bioscience · 2025Review
- FFAR4-mediated IL-6 release from islet macrophages promotes insulin secretion and is compromised in type-2 diabetes.Nature communications · 2025Article
- Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.International journal of molecular sciences · 2025Review
- GPR132 regulates the function of NK cells through the Gαs/CSK/ZAP70/NF-κB signaling pathway as a potential immune checkpoint.Science advances · 2025Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Chronic inflammation due to islet-residing macrophages plays key roles in the development of type 2 diabetes mellitus. By systematically profiling intra-islet lipid-transmembrane receptor signalling in islet-resident macrophages, we identified endogenous 9(S)-hydroxy-10,12-octadecadienoic acid-G-protein-coupled receptor 132 (GPR132)-Gi signalling as a significant contributor to islet macrophage reprogramming and found that GPR132 deficiency in macrophages reversed metabolic disorders in mice fed a high-fat diet. The cryo-electron microscopy structures of GPR132 bound with two endogenous agonists, N-palmitoylglycine and 9(S)-hydroxy-10,12-octadecadienoic acid, enabled us to rationally design both GPR132 agonists and antagonists with high potency and selectivity through stepwise translational approaches. We ultimately identified a selective GPR132 antagonist, NOX-6-18, that modulates macrophage reprogramming within pancreatic islets, decreases weight gain and enhances glucose metabolism in mice fed a high-fat diet. Our study not only illustrates that intra-islet lipid signalling contributes to islet macrophage reprogramming but also provides a broadly applicable strategy for the identification of important G-protein-coupled receptor targets in pathophysiological processes, followed by the rational design of therapeutic leads for refractory diseases such as diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.