ArticleDiabetologia2011
The dicarboxylate carrier plays a role in mitochondrial malate transport and in the regulation of glucose-stimulated insulin secretion from rat pancreatic beta cells.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Mitochondrial succinate transport is required for cardiac ischaemia/reperfusion injury.Cardiovascular research · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Inhibition of SLC25A10 promotes cellular senescence and impedes hepatocellular carcinoma progression.Translational cancer research · 2025Article
- Unlocking the Power of Magnesium: A Systematic Review and Meta-Analysis Regarding Its Role in Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2025Review
- The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.International journal of molecular sciences · 2024Review
- [Latest Findings on the Role of α-Ketoglutarate in Metabolic Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Metabolic cycles and signals for insulin secretion.Cell metabolism · 2022Review
- Oxidative Stress Related to Plasmalemmal and Mitochondrial Phosphate Transporters in Vascular Calcification.Antioxidants (Basel, Switzerland) · 2022Review
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
- The mitochondrial dicarboxylate carrier prevents hepatic lipotoxicity by inhibiting white adipocyte lipolysis.Journal of hepatology · 2021Article
- Heterologous Expression of Two Malate Transporters From an Oleaginous FungusFrontiers in microbiology · 2021Article
- SLC25A10 performs an oncogenic role in human osteosarcoma.Oncology letters · 2020Article
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Mitochondrial Citrate Transport System in the Fungus Mucor circinelloides: Identification, Phylogenetic Analysis, and Expression Profiling During Growth and Lipid Accumulation.Current microbiology · 2020Article
- 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 Loss of ARNT/HIF1β in Male Pancreatic β-Cells Is Protective Against High-Fat Diet-Induced Diabetes.Endocrinology · 2019Article
- Integrated In Vivo Quantitative Proteomics and Nutrient Tracing Reveals Age-Related Metabolic Rewiring of Pancreatic β Cell Function.Cell reports · 2018Article
- Functional Properties of the Mitochondrial Carrier System.Trends in cell biology · 2017Review
- Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion.Physiological reports · 2016Article
- Measurement of the Absolute Magnitude and Time Courses of Mitochondrial Membrane Potential in Primary and Clonal Pancreatic Beta-Cells.PloS one · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisWe have previously described a strong correlation between pyruvate cycling and insulin secretion. We have also demonstrated a particularly important role for a pyruvate-isocitrate cycling pathway involving the mitochondrial citrate/isocitrate carrier (CIC) and cytosolic NADP-dependent isocitrate dehydrogenase. CIC requires cytosolic malate as a counter-substrate during citrate and isocitrate export. Thus, considering that the mitochondrial dicarboxylate carrier (DIC) provides an important source of cytosolic malate, we investigated the potential role of DIC in control of glucose-stimulated insulin secretion (GSIS).
methodsWe used pharmacological and small interfering RNA (siRNA) tools to assess the role of DIC in insulin release in clonal insulin-secreting 832/13 cells and isolated rat islets.
resultsButylmalonate, an inhibitor of malate transport, reduced cytosolic malate and citrate levels, and inhibited GSIS in a dose-dependent manner in 832/13 cells. Suppression of DIC expression resulted in inhibition of GSIS by 5% to 69%, the extent of inhibition of insulin secretion being proportional to the level of Dic (also known as Slc25a10) gene knockdown. The most effective siRNA duplex against Dic did not affect glucose utilisation, glucose oxidation or ATP/ADP ratio, but did suppress glucose-induced increments of the NADPH/NADP(+) ratio. Confirmation of our results in primary cultures of isolated rat islets showed that butylmalonate and an adenovirus expressing an siRNA against Dic-inhibited GSIS. CONCLUSIONS/
interpretationMalate transport by DIC may play an important role in GSIS, possibly by providing cytosolic malate as a counter-substrate for citrate and/or isocitrate export by CIC. These studies also suggest that malate transport by DIC is (1) a critical component of NADPH production mediated by pyruvate-cycling and (2) regulates GSIS.
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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.