ArticleCell reports2014
Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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Who cites it
87 citing papers in PubMed, 154 citations in OpenAlex.
- Effects of dextromethorphan as add-on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blinded, multiple crossover, single-dose clinical trial.Diabetes, obesity & metabolism · 2016Trial
- Review
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- Binge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells.Nature communications · 2025Article
- Regulation of L-Lactate in Glutamate Excitotoxicity Under Cerebral Ischemia: Pathophysiology and Preventive Strategy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Improving cellular fitness of human stem cell-derived islets under hypoxia.Nature communications · 2025Article
- Proline exacerbates hepatic gluconeogenesis via paraspeckle-dependent mRNA retention.Nature metabolism · 2025Article
- 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
- Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- The Regulation Role of the Gut-Islets Axis in Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Liver Metabolomics and Inflammatory Profiles in Mouse Model of Fentanyl Overdose Treated with Beta-Lactams.Metabolites · 2023Article
- Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy.International journal of molecular sciences · 2023Article
- Article
- Pancreatic β-cell glutaminase 2 maintains glucose homeostasis under the condition of hyperglycaemia.Scientific reports · 2023Article
- Exploring the aging process of cognitively healthy adults by analyzing cerebrospinal fluid metabolomics using liquid chromatography-tandem mass spectrometry.BMC geriatrics · 2023Article
- Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.Frontiers in endocrinology · 2023Article
- The Critical Biomarkers Identification of Insulin Signaling Involved in Initiating cAMP Signaling Mediated Salivary Secretion in Sjogren Syndrome: Transcriptome Sequencing in NOD Mice Model.Biological procedures online · 2022Article
- Roles and Mechanisms of Astragaloside IV in Combating Neuronal Aging.Aging and disease · 2022Review
- Metabolomics in Diabetic Retinopathy: From Potential Biomarkers to Molecular Basis of Oxidative Stress.Cells · 2022Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Incretins, hormones released by the gut after meal ingestion, are essential for maintaining systemic glucose homeostasis by stimulating insulin secretion. The effect of incretins on insulin secretion occurs only at elevated glucose concentrations and is mediated by cAMP signaling, but the mechanism linking glucose metabolism and cAMP action in insulin secretion is unknown. We show here, using a metabolomics-based approach, that cytosolic glutamate derived from the malate-aspartate shuttle upon glucose stimulation underlies the stimulatory effect of incretins and that glutamate uptake into insulin granules mediated by cAMP/PKA signaling amplifies insulin release. Glutamate production is diminished in an incretin-unresponsive, insulin-secreting β cell line and pancreatic islets of animal models of human diabetes and obesity. Conversely, a membrane-permeable glutamate precursor restores amplification of insulin secretion in these models. Thus, cytosolic glutamate represents the elusive link between glucose metabolism and cAMP action in incretin-induced insulin secretion.
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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.