ArticlePloS one2013
A role for cytosolic isocitrate dehydrogenase as a negative regulator of glucose signaling for insulin secretion in pancreatic ß-cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- The glucose-lowering effect of low-dose diacerein and its responsiveness metabolic markers in uncontrolled diabetes.BMC research notes · 2022Trial
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
- Metabolic and Molecular Amplification of Insulin Secretion.Advances in anatomy, embryology, and cell biology · 2024Review
- NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.iScience · 2023Article
- Article
- Ensemble-based genome-scale modeling predicts metabolic differences between macrophage subtypes in colorectal cancer.bioRxiv : the preprint server for biology · 2023Article
- Metabolic stress-induced human beta-cell death is mediated by increased intracellular levels of adenosine.Frontiers in endocrinology · 2023Article
- A pathway model of glucose-stimulated insulin secretion in the pancreaticFrontiers in endocrinology · 2023Article
- Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion.PLoS computational biology · 2022Article
- A proteomics approach to decipher a sticky CHO situation.Biotechnology and bioengineering · 2022Article
- Metabolic cycles and signals for insulin secretion.Cell metabolism · 2022Review
- Maturation of beta cells: lessons from in vivo and in vitro models.Diabetologia · 2022Review
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Using recombinase-mediated cassette exchange to engineer MIN6 insulin-secreting cells based on a newly identified safe harbor locus.Journal of diabetes investigation · 2021Article
- Review
- Mechanisms controlling pancreatic islet cell function in insulin secretion.Nature reviews. Molecular cell biology · 2021Review
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- Nrf2: The Master and Captain of Beta Cell Fate.Trends in endocrinology and metabolism: TEM · 2021Review
- Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.Diabetologia · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Cytosolic NADPH may act as one of the signals that couple glucose metabolism to insulin secretion in the pancreatic ß-cell. NADPH levels in the cytoplasm are largely controlled by the cytosolic isoforms of malic enzyme and isocitrate dehydrogenase (IDHc). Some studies have provided evidence for a role of malic enzyme in glucose-induced insulin secretion (GIIS) via pyruvate cycling, but the role of IDHc in ß-cell signaling is unsettled. IDHc is an established component of the isocitrate/α-ketoglutarate shuttle that transfers reducing equivalents (NADPH) from the mitochondrion to the cytosol. This shuttle is energy consuming since it is coupled to nicotinamide nucleotide transhydrogenase that uses the mitochondrial proton gradient to produce mitochondrial NADPH and NAD(+) from NADP(+) and NADH. To determine whether flux through IDHc is positively or negatively linked to GIIS, we performed RNAi knockdown experiments in ß-cells. Reduced IDHc expression in INS 832/13 cells and isolated rat islet ß-cells resulted in enhanced GIIS. This effect was mediated at least in part via the KATP-independent amplification arm of GIIS. IDHc knockdown in INS 832/13 cells did not alter glucose oxidation but it reduced fatty acid oxidation and increased lipogenesis from glucose. Metabolome profiling in INS 832/13 cells showed that IDHc knockdown increased isocitrate and NADP(+) levels. It also increased the cellular contents of several metabolites linked to GIIS, in particular some Krebs cycle intermediates, acetyl-CoA, glutamate, cAMP and ATP. The results identify IDHc as a component of the emerging pathways that negatively regulate GIIS.
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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.