ArticleCell metabolism2021
Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion.
Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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85 citing papers in PubMed, 145 citations in OpenAlex.
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- α-Ketoglutarate accelerates cutaneous wound healing through modulating the epithelial-fibroblast niche.JCI insight · 2026Article
- Glutamine Metabolism in Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2026Review
- IDH2 lactylation regulates mitochondrial dysfunction injury induced by myocardial ischemia‑reperfusion via the AMPK signaling pathway.International journal of molecular medicine · 2026Article
- Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis.Nature aging · 2026Article
- Glutamine metabolic stress induces SLC25A6-dependent mitofission via MIC60-MIC19 complex disassembly in colorectal cancer.Cell death & disease · 2026Article
- AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression.Cell death & disease · 2026Article
- Modifying muscle metabolic dysregulation in inclusion body myositis with pioglitazone: a single-arm trial.Nature communications · 2026Article
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- NFS1 Regulates IDH2 to Attenuate Abdominal Aortic Aneurysms via Interacting With SP2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated DIA proteomics and transcriptomics unravel molecular mechanisms of uterine prolificacy in Yunshang Black goats during the estrous cycle.BMC genomics · 2026Article
- Effects of L-citrulline supplementation in the basal diet on reproductive performance, serum metabolites, and microbial community structure in Simmental cows.Frontiers in microbiology · 2026Article
- Mapping carbon utilization pathways inmSystems · 2025Article
- Metabolism and HSC fate: what NADPH is made for.Trends in cell biology · 2025Review
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- Improvement of Quality of Sour Camel Milk by Extract ofFoods (Basel, Switzerland) · 2025Article
- LPS mediates cuproptosis and inflammation in THP-1 macrophages through HKDC1.Acta biochimica et biophysica Sinica · 2025Article
- HDAC7 promotes renal cancer progression by reprogramming branched-chain amino acid metabolism.Science advances · 2025Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Metabolic fuels regulate insulin secretion by generating second messengers that drive insulin granule exocytosis, but the biochemical pathways involved are incompletely understood. Here we demonstrate that stimulation of rat insulinoma cells or primary rat islets with glucose or glutamine + 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (Gln + BCH) induces reductive, "counter-clockwise" tricarboxylic acid (TCA) cycle flux of glutamine to citrate. Molecular or pharmacologic suppression of isocitrate dehydrogenase-2 (IDH2), which catalyzes reductive carboxylation of 2-ketoglutarate to isocitrate, results in impairment of glucose- and Gln + BCH-stimulated reductive TCA cycle flux, lowering of NADPH levels, and inhibition of insulin secretion. Pharmacologic suppression of IDH2 also inhibits insulin secretion in living mice. Reductive TCA cycle flux has been proposed as a mechanism for generation of biomass in cancer cells. Here we demonstrate that reductive TCA cycle flux also produces stimulus-secretion coupling factors that regulate insulin secretion, including in non-dividing cells.
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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.