ArticleThe Journal of biological chemistry2009
Mitochondrial glutamate carrier GC1 as a newly identified player in the control of glucose-stimulated insulin secretion.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Synergistic protective effects of TCM formula NRICM102 andFrontiers in pharmacology · 2025Article
- Glutamine Metabolism and Prostate Cancer.Cancers · 2024Review
- Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer.Nature communications · 2023Article
- Role of Mitochondrial Transporters on Metabolic Rewiring of Pancreatic Adenocarcinoma: A Comprehensive Review.Cancers · 2023Review
- Metabolism-secretion coupling in glucose-stimulated insulin secretion.Diabetology international · 2022Review
- Tumor necrosis factor induces pathogenic mitochondrial ROS in tuberculosis through reverse electron transport.Science (New York, N.Y.) · 2022Article
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.Biomolecules · 2022Review
- Article
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress.Biomolecules · 2020Article
- Review
- Mitochondrial Carriers for Aspartate, Glutamate and Other Amino Acids: A Review.International journal of molecular sciences · 2019Review
- Glutamate as intracellular and extracellular signals in pancreatic islet functions.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- MiR-184 expression is regulated by AMPK in pancreatic islets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- SLC25A22 Promotes Proliferation and Metastasis of Osteosarcoma Cells via the PTEN Signaling Pathway.Technology in cancer research & treatment · 2018Article
- Inhibition of the Mitochondrial Glutamate Carrier SLC25A22 in Astrocytes Leads to Intracellular Glutamate Accumulation.Frontiers in cellular neuroscience · 2017Article
- The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity.The Journal of biological chemistry · 2016Article
- β-Cell glutamate signaling: Its role in incretin-induced insulin secretion.Journal of diabetes investigation · 2016Review
- miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SLC25 carrier family mediates solute transport across the inner mitochondrial membrane, a process that is still poorly characterized regarding both the mechanisms and proteins implicated. This study investigated mitochondrial glutamate carrier GC1 in insulin-secreting beta-cells. GC1 was cloned from insulin-secreting cells, and sequence analysis revealed hydropathy profile of a six-transmembrane protein, characteristic of mitochondrial solute carriers. GC1 was found to be expressed at the mRNA and protein levels in INS-1E beta-cells and pancreatic rat islets. Immunohistochemistry showed that GC1 was present in mitochondria, and ultrastructural analysis by electron microscopy revealed inner mitochondrial membrane localization of the transporter. Silencing of GC1 in INS-1E beta-cells, mediated by adenoviral delivery of short hairpin RNA, reduced mitochondrial glutamate transport by 48% (p < 0.001). Insulin secretion at basal 2.5 mM glucose and stimulated either by intermediate 7.5 mM glucose or non-nutrient 30 mM KCl was not modified by GC1 silencing. Conversely, insulin secretion stimulated with optimal 15 mM glucose was reduced by 23% (p < 0.005) in GC1 knocked down cells compared with controls. Adjunct of cell-permeant glutamate (5 mM dimethyl glutamate) fully restored the secretory response at 15 mM glucose (p < 0.005). Kinetics of insulin secretion were investigated in perifused isolated rat islets. GC1 silencing in islets inhibited the secretory response induced by 16.7 mM glucose, both during first (-25%, p < 0.05) and second (-33%, p < 0.05) phases. This study demonstrates that insulin-secreting cells depend on GC1 for maximal glucose response, thereby assigning a physiological function to this newly identified mitochondrial glutamate carrier.
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