ArticleThe Journal of biological chemistry2014
Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 105 citations in OpenAlex.
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Bacterial pyruvate metabolism regulates host insulin sensitivity inbioRxiv : the preprint server for biology · 2026Article
- The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.Islets · 2025Article
- MCT1-mediated Lactate Shuttle to Mitochondria Governs Macrophage Polarization and Modulates Glucose Homeostasis by Affecting β Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications.Biomolecules · 2025Review
- The impact of metabolic reprogramming in hepatocellular carcinoma on T cell.Frontiers in immunology · 2025Review
- Integrative proteomics and metabolomics analysis of the mechanism of pancreatic β-cell dysfunction in aged mice.Frontiers in endocrinology · 2025Article
- Tissue derivatization for visualizing lactate and pyruvate in mouse testis tissues using matrix-assisted laser desorption/ionization-mass spectrometry imaging.Analytical and bioanalytical chemistry · 2024Article
- Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells.Stem cell research & therapy · 2024Article
- Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling.Frontiers in bioengineering and biotechnology · 2024Article
- Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.Frontiers in cardiovascular medicine · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Glycolytic System in Axons Supplement Decreased ATP Levels after Axotomy of the Peripheral Nerve.eNeuro · 2023Article
- Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the 'Bystander' Activation of Memory CD8International journal of molecular sciences · 2023Review
- Metabolic Profiling of Pregnant Women with Obesity: An Exploratory Study in Women at Greater Risk of Gestational Diabetes.Metabolites · 2022Article
- Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier.Nutrients · 2022Article
- The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.American journal of physiology. Endocrinology and metabolism · 2022Review
- Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids.Frontiers in medicine · 2022Article
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
It is well known that mitochondrial metabolism of pyruvate is critical for insulin secretion; however, we know little about how pyruvate is transported into mitochondria in β-cells. Part of the reason for this lack of knowledge is that the carrier gene was only discovered in 2012. In the current study, we assess the role of the recently identified carrier in the regulation of insulin secretion. Our studies show that β-cells express both mitochondrial pyruvate carriers (Mpc1 and Mpc2). Using both pharmacological inhibitors and siRNA-mediated knockdown of the MPCs we show that this carrier plays a key role in regulating insulin secretion in clonal 832/13 β-cells as well as rat and human islets. We also show that the MPC is an essential regulator of both the ATP-regulated potassium (KATP) channel-dependent and -independent pathways of insulin secretion. Inhibition of the MPC blocks the glucose-stimulated increase in two key signaling molecules involved in regulating insulin secretion, the ATP/ADP ratio and NADPH/NADP(+) ratio. The MPC also plays a role in in vivo glucose homeostasis as inhibition of MPC by the pharmacological inhibitor α-cyano-β-(1-phenylindol-3-yl)-acrylate (UK5099) resulted in impaired glucose tolerance. These studies clearly show that the newly identified mitochondrial pyruvate carrier sits at an important branching point in nutrient metabolism and that it is an essential regulator of 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.