ArticleJCI insight2021
Gq signaling in α cells is critical for maintaining euglycemia.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication.Cell metabolism · 2025Article
- Dehydration-induced AVP stimulates glucagon release and ketogenesis.American journal of physiology. Endocrinology and metabolism · 2025Article
- Article
- Commentary on "Intra-islet α-cell Gs signaling promotes glucagon release".Journal of diabetes investigation · 2024Article
- Beyond Expected Patterns in Insulin Needs of People With Type 1 Diabetes: Temporal Analysis of Automated Insulin Delivery Data.JMIRx med · 2024Article
- Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease.American journal of physiology. Endocrinology and metabolism · 2024Review
- V1bR enhances glucose-stimulated insulin secretion by paracrine production of glucagon which activates GLP-1 receptor.Cell & bioscience · 2024Article
- Intra-islet α-cell Gs signaling promotes glucagon release.Nature communications · 2024Article
- GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.Peptides · 2024Article
- Article
- Time-dependent effects of endogenous hyperglucagonemia on glucose homeostasis and hepatic glucagon action.JCI insight · 2023Article
- GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.Frontiers in endocrinology · 2023Review
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Sex and gender differences in community-acquired pneumonia.Internal and emergency medicine · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Glucagon, a hormone released from pancreatic α cells, plays a key role in maintaining euglycemia. New insights into the signaling pathways that control glucagon secretion may stimulate the development of novel therapeutic agents. In this study, we investigated the potential regulation of α cell function by G proteins of the Gq family. The use of a chemogenetic strategy allowed us to selectively activate Gq signaling in mouse α cells in vitro and in vivo. Acute stimulation of α cell Gq signaling led to elevated plasma glucagon levels, accompanied by increased insulin release and improved glucose tolerance. Moreover, chronic activation of this pathway greatly improved glucose tolerance in obese mice. We also identified an endogenous Gq-coupled receptor (vasopressin 1b receptor; V1bR) that was enriched in mouse and human α cells. Agonist-induced activation of the V1bR strongly stimulated glucagon release in a Gq-dependent fashion. In vivo studies indicated that V1bR-mediated glucagon release played a key role in the counterregulatory hyperglucagonemia under hypoglycemic and glucopenic conditions. These data indicate that α cell Gq signaling represents an important regulator of glucagon secretion, resulting in multiple beneficial metabolic effects. Thus, drugs that target α cell-enriched Gq-coupled receptors may prove useful to restore euglycemia in various pathophysiological conditions.
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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.