ArticleDiabetologia2024
ADGRL1 is a glucose receptor involved in mediating energy and glucose homeostasis.
Article in Diabetologia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Therapeutic targeting of adhesion GPCRs: a status update and future potential.Expert opinion on drug discovery · 2026Review
- Contribution of metabolism-independent glucose sensing to metabolic homeostasis.Trends in endocrinology and metabolism: TEM · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Brain Nutrient Sensing: A Unifying Framework.Annual review of physiology · 2026Review
- Orphan GPCRs in diabetes mellitus: metabolic control, inflammation, and drug development.Frontiers in endocrinology · 2026Review
- Developmental programming: Differing impact of prenatal testosterone and prenatal bisphenol-A -treatment on hepatic methylome in female sheep.Molecular and cellular endocrinology · 2025Article
- GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4.General and comparative endocrinology · 2025Article
- Sugar-sensing swodkoreceptors and swodkocrine signaling.Animal models and experimental medicine · 2025Article
- Glucose sensing and homeostasis by adipocyte GPCR.Frontiers in endocrinology · 2025Review
- Adhesion G protein-coupled receptor latrophilin 1 (ADGRL1): a novel regulator of glucose and energy homeostasis.Signal transduction and targeted therapy · 2024Article
- Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity.Signal transduction and targeted therapy · 2024Article
- A protocol to isolate, identify, and verify glucose- or carbohydrate-binding receptors.Biology methods & protocols · 2024Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.
methodsHere we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to proteomic analyses and identified adhesion G-protein coupled receptor 1 (ADGRL1) as a top candidate for a glucose receptor. We validated glucose-ADGRL1 interactions using CHO cells stably expressing human ADGRL1 and ligand-receptor binding assays. We generated and determined the phenotype of global Adgrl1-knockout mice and hypothalamus-specific Adgrl1-deficient mice. We measured the variables related to glucose and energy homeostasis in these mice. We also generated an Adgrl1
resultsAdgrl1 is highly expressed in the ventromedial nucleus of the hypothalamus (VMH) in mice. Lack of Adgrl1 in the VMH in mice caused fasting hyperinsulinaemia, enhanced glucose-stimulated insulin secretion and insulin resistance. In addition, the Adgrl1-deficient mice had impaired feeding responses to glucose and fasting coupled with abnormal glucose sensing and decreased physical activity before development of obesity and hyperglycaemia. In female mice, ovariectomy was necessary to reveal the contribution of ADGRL1 to energy and glucose homeostasis. CONCLUSIONS/
interpretationAltogether, our findings demonstrate that ADGRL1 binds glucose and is involved in energy as well as glucose homeostasis in a sex-dependent manner. Targeting ADGRL1 may introduce a new class of drugs for the treatment of type 2 diabetes and obesity.
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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 Socratic graph.