ArticleCell metabolism2008
Glutamate is a positive autocrine signal for glucagon release.
Article in Cell metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 217 citations in OpenAlex.
- Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men.Diabetologia · 2009Trial
- Article
- Antecedent hypoglycaemia impairs glucagon secretion by enhancing somatostatin-mediated negative feedback control.Nature metabolism · 2026Article
- Efficacy of Dual Glucagon and GLP-1 Agonists as New Treatments for Type II Diabetes.Mini reviews in medicinal chemistry · 2026Review
- Review
- Neurotransmitter Alterations in Prediabetes and Type 2 Diabetes Mellitus: A Narrative Review.International journal of molecular sciences · 2025Review
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Circulating amino acid signature features urea cycle alterations associated with coronary artery disease.Scientific reports · 2024Observational
- Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling.Diabetes · 2024Article
- Hyperglycemia impairs EAAT2 glutamate transporter trafficking and glutamate clearance in islets of Langerhans: implications for type 2 diabetes pathogenesis and treatment.American journal of physiology. Endocrinology and metabolism · 2024Article
- The anterior chamber of the eye technology and its anatomical, optical, and immunological bases.Physiological reviews · 2024Review
- Paracrine Signaling by Pancreatic Islet Cilia.Current opinion in endocrine and metabolic research · 2024Article
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
- Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.PloS one · 2024Article
- The role of GABA in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Metabolic regulation of glucagon secretion.The Journal of endocrinology · 2023Article
- Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas.Nature metabolism · 2023Article
- α-cell electrophysiology and the regulation of glucagon secretion.The Journal of endocrinology · 2023Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic alpha cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human alpha cells express ionotropic glutamate receptors (iGluRs) that are essential for glucagon release. A lowering in glucose concentration results in the release of glutamate from the alpha cell. Glutamate then acts on iGluRs of the AMPA/kainate type, resulting in membrane depolarization, opening of voltage-gated Ca(2+) channels, increase in cytoplasmic free Ca(2+) concentration, and enhanced glucagon release. In vivo blockade of iGluRs reduces glucagon secretion and exacerbates insulin-induced hypoglycemia in mice. Hence, the glutamate autocrine feedback loop endows the alpha cell with the ability to effectively potentiate its own secretory activity. This is a prerequisite to guarantee adequate glucagon release despite relatively modest changes in blood glucose concentration under physiological 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.