ArticlePloS one2011
A role for glutamate transporters in the regulation of insulin secretion.
Article in PloS one, 2011. 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, 58 citations in OpenAlex.
- Integrated biophysical and spatial remodeling during insulin secretory granule maturation at the mitochondrial network.bioRxiv : the preprint server for biology · 2026Article
- Hippocampal-Specific Insulin Resistance Elicits Synaptic Effects on Glutamate Neurotransmission.Journal of neurochemistry · 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
- Pancreatic β-cell glutaminase 2 maintains glucose homeostasis under the condition of hyperglycaemia.Scientific reports · 2023Article
- Metabolism-secretion coupling in glucose-stimulated insulin secretion.Diabetology international · 2022Review
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour.International journal of molecular sciences · 2022Review
- Article
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- Factors Influencing Mitochondrial Function as a Key Mediator of Glucose-Induced Insulin Release: Highlighting Nicotinamide Nucleotide Transhydrogenase.International journal of molecular and cellular medicine · 2020Review
- The glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging.Molecular metabolism · 2019Article
- Glutamate as intracellular and extracellular signals in pancreatic islet functions.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- The UBR-1 ubiquitin ligase regulates glutamate metabolism to generate coordinated motor pattern in Caenorhabditis elegans.PLoS genetics · 2018Article
- Contribution of Vesicular Glutamate Transporters to Stress Response and Related Psychopathologies: Studies in VGluT3 Knockout Mice.Cellular and molecular neurobiology · 2018Review
- Autocrine, paracrine and necrotic NMDA receptor signalling in mouse pancreatic neuroendocrine tumour cells.Open biology · 2017Article
- NMDA receptors mediate leptin signaling and regulate potassium channel trafficking in pancreatic β-cells.The Journal of biological chemistry · 2017Article
- Article
- β-Cell glutamate signaling: Its role in incretin-induced insulin secretion.Journal of diabetes investigation · 2016Review
- Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 5 countries.
Funding
Abstract
In the brain, glutamate is an extracellular transmitter that mediates cell-to-cell communication. Prior to synaptic release it is pumped into vesicles by vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor responses after release, glutamate is taken up into glial cells or neurons by excitatory amino acid transporters (EAATs). In the pancreatic islets of Langerhans, glutamate is proposed to act as an intracellular messenger, regulating insulin secretion from β-cells, but the mechanisms involved are unknown. By immunogold cytochemistry we show that insulin containing secretory granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of glutamate in these granules are low, indicating the presence of a protein that can transport glutamate out of the granules. Surprisingly, in β-cells the glutamate transporter EAAT2 is located, not in the plasma membrane as it is in brain cells, but exclusively in insulin-containing secretory granules, together with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory granules is higher than in wild type mice. These data imply a glutamate cycle in which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2. Perturbing this cycle by knocking down EAAT2 expression with a small interfering RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly reduced the rate of granule exocytosis. Simulations of granule energetics suggest that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules and thereby regulate insulin secretion. These data suggest that insulin secretion from β-cells is modulated by the flux of glutamate through the secretory granules.
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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.