ArticleCell metabolism2020
Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health.
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Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The efficacy and safety of qiwei baizhu san in the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging.Nature aging · 2026Article
- Mitochondrial control of glycerolipid synthesis by a PEP shuttle.bioRxiv : the preprint server for biology · 2026Article
- Article
- Pancreatic islet cell calcium ion imaging at single-cell resolution: functional identification of first-responder, highly connected ("hub"), and leader beta-cells.Frontiers in endocrinology · 2026Review
- Phospho-enol pyruvate carboxykinase inhibition limits effector function in inflammatory T cells.Frontiers in immunology · 2026Article
- The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.Islets · 2025Article
- Amino acid sensing by the α-cell mitochondrial phosphoenolpyruvate cycle regulates intracellular CabioRxiv : the preprint server for biology · 2025Article
- Pyruvate kinase modulates the link between β-cell fructose metabolism and insulin secretion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Stimulus-Secretion Coupling Mechanisms of Glucose-Induced Insulin Secretion: Biochemical Discrepancies Among the Canonical, ADP Privation, and GABA-Shunt Models.International journal of molecular sciences · 2025Review
- The Synergistic Impact of Glycolysis, Mitochondrial OxPhos, and PEP Cycling on ATP Production in Beta Cells.International journal of molecular sciences · 2025Article
- FicD sensitizes cellular response to glucose fluctuations in mouse embryonic fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Do We Need a New Hypothesis for KATP Closure in β-Cells? Distinguishing the Baby From the Bathwater.Diabetes · 2024Article
- Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver.Advanced healthcare materials · 2024Article
- Metabolic and Molecular Amplification of Insulin Secretion.Advances in anatomy, embryology, and cell biology · 2024Review
- Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling.Frontiers in bioengineering and biotechnology · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- A Defect in Mitochondrial Complex III but Not in Complexes I or IV Causes Early β-Cell Dysfunction and Hyperglycemia in Mice.Diabetes · 2023Article
- Article
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Authors and funding
18 authors.
Abudukadier AbuliziDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Rebecca L CardoneDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Romana StarkDepartment of Physiology, Monash University, Melbourne, VIC 3800, Australia.
Sophie L LewandowskiDepartment of Medicine, Division of Endocrinology, Diabetes, and Metabolism, and Department of Biomolecular Chemistry, University of Wisconsin-Madison, and William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Xiaojian ZhaoDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Joelle HillionDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Lingjun MaDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Raghav SehgalDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Tiago C AlvesDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Craig ThomasDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, and Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Charles KungAgios Pharmaceuticals, Cambridge, MA 02139, USA.
Bei WangDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Stephan SiebelDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA.
Zane B AndrewsDepartment of Physiology, Monash University, Melbourne, VIC 3800, Australia.
Graeme F MasonDepartment of Diagnostic Radiology and Psychiatry, Yale University, New Haven, CT 06520, USA.
Jesse RinehartDepartment of Cellular & Molecular Physiology, Yale University, New Haven, CT 06520, USA.
Matthew J MerrinsDepartment of Medicine, Division of Endocrinology, Diabetes, and Metabolism, and Department of Biomolecular Chemistry, University of Wisconsin-Madison, and William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Richard G KibbeyDepartment of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular & Molecular Physiology, Yale University, New Haven, CT 06520, USA. Electronic address: richard.kibbey@yale.edu.
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MYALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAMUL1RR024139 · NCRR · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2006 to 2011
$56.8MYale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0MYale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1MTRAINING IN NUTRITIONT32DK007665 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI GUY E GROBLEWSKI, Chi- Liang Eric Yen · 1993 to 2026
$9.2MMitochondrial ADP privation: A unifying model for glucose-induced insulin secretion.R01DK127637 · NIDDK · YALE UNIVERSITY · PI KIBBEY, RICHARD G, MERRINS, MATTHEW J. · 2021 to 2025
$3.4MMetabolic Functions of Pyruvate Kinase M2 in Pancreatic Beta CellsR01DK113103 · NIDDK · YALE UNIVERSITY · PI Matthew J. Merrins · 2017 to 2026
$3.3MComprehensive, Cross Platform-Validated 13C Flux Measures of Intra-and Inter-tissue MetabolismR01DK108283 · NIDDK · YALE UNIVERSITY · PI KIBBEY, RICHARD G, MASON, GRAEME F. · 2016 to 2019
$2.1MComparative analysis of geroprotective interventions in established and novel mouse models of Alzheimer's diseaseR01AG062328 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM, MERRINS, MATTHEW J. · 2018 to 2022
$2.0MThe role of the mitochondrial GTP cycle in insulin secretionR01DK092606 · NIDDK · YALE UNIVERSITY · PI KIBBEY, RICHARD G · 2011 to 2015
$1.8MChastening the double-edged sword of glucose metabolism in beta-cellsR01DK110181 · NIDDK · YALE UNIVERSITY · PI KIBBEY, RICHARD G · 2016 to 2019
$1.7MCharacterization of Mitochondrial GTP as an Intramitochondrial Metabolic SignalK08DK080142 · NIDDK · YALE UNIVERSITY · PI KIBBEY, RICHARD G · 2008 to 2012
$763kNCATS NIH HHS UL1 TR001863NCRR NIH HHS UL1 RR024139NIA NIH HHS R01 AG062328NIA NIH HHS R21 AG050135NIDDK NIH HHS F31 DK126403NIDDK NIH HHS K01 DK101683NIDDK NIH HHS K08 DK080142NIDDK NIH HHS P30 DK034989NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK092606NIDDK NIH HHS R01 DK108283NIDDK NIH HHS R01 DK110181NIDDK NIH HHS R01 DK113103NIDDK NIH HHS R01 DK127637NIDDK NIH HHS T32 DK007665
Abstract
The mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle couples mitochondrial PEPCK (PCK2) to pyruvate kinase (PK) in the liver and pancreatic islets to regulate glucose homeostasis. Here, small molecule PK activators accelerated the PEP cycle to improve islet function, as well as metabolic homeostasis, in preclinical rodent models of diabetes. In contrast, treatment with a PK activator did not improve insulin secretion in pck2
Indexed as
AnimalsHomeostasisInsulinMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaPhosphoenolpyruvatePyruvate KinaseRatsRats, Sprague-DawleyInsulinPhosphoenolpyruvatePyruvate Kinaseanaplerosiscataplerosisfatty liverhuman isletsinsulin resistanceinsulin secretionmitochondrial GTPmitochondrial PEPCKphosphoenolpyruvate cyclepyruvate kinase
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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.