ArticleMolecular metabolism2016
An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- 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
- Mitochondrial Pyruvate Metabolism Controls Alveolar Stem Cell Fate and Inflammatory Balance.Inflammation · 2026Article
- Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila.iScience · 2025Article
- Transgenic Cotton Expressing dsInternational journal of molecular sciences · 2024Article
- Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer's Disease Implications.Life (Basel, Switzerland) · 2024Review
- Mitochondria: a new intervention target for tumor invasion and metastasis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Computational structural prediction and chemical inhibition of the human mitochondrial pyruvate carrier protein heterodimer complex.bioRxiv : the preprint server for biology · 2024Article
- Glycogen homeostasis and mtDNA expression require motor neuron to muscle TGFβ/Activin Signaling inbioRxiv : the preprint server for biology · 2024Article
- Sex-dependent adipose glucose partitioning by the mitochondrial pyruvate carrier.bioRxiv : the preprint server for biology · 2024Article
- The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.American journal of physiology. Endocrinology and metabolism · 2022Review
- Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells.Oncology reports · 2022Article
- Metabolic Mechanisms Connecting Alzheimer's and Parkinson's Diseases: Potential Avenues for Novel Therapeutic Approaches.Frontiers in molecular biosciences · 2022Review
- Review
- Heart failure-emerging roles for the mitochondrial pyruvate carrier.Cell death and differentiation · 2021Review
- The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis.Cancers · 2021Review
- Mechanical Permeabilization as a New Method for Assessment of Mitochondrial Function in Insect Tissues.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.Diabetologia · 2020Article
- Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice.Nature metabolism · 2020Article
- Role of the Mitochondrial Pyruvate Carrier in the Occurrence of Metabolic Inflexibility inMetabolites · 2020Article
- Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency inMetabolites · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveTransport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC) is an important and rate-limiting step in its metabolism. In pancreatic β-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion.
methodsTo evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells.
resultsIn both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, β-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP) channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity.
conclusionsAltogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia.
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Registered trials
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