ArticleThe Journal of clinical investigation2015
Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 174 citations in OpenAlex.
- The glucose-lowering effect of low-dose diacerein and its responsiveness metabolic markers in uncontrolled diabetes.BMC research notes · 2022Trial
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Metabolite Genome-Wide Association in Hispanics with Obesity Reveals Genetic Risk and Interactions with Dietary Factors for Type 2 Diabetes.Metabolites · 2025Article
- Curcumin-loaded bioadhesive silk fibroin microsphere improves islet transplantation by mitigating oxidative stress and inhibiting apoptosis.Materials today. Bio · 2025Article
- Review
- Diagnostic and Therapeutic Implications of the SUMOylation Pathway in Acute Myeloid Leukemia.Cancers · 2025Review
- Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.Life science alliance · 2024Article
- Effects of novel flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPhP) on function and homeostasis in human and rat pancreatic beta-cell lines.Archives of toxicology · 2024Article
- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- Checkpoint kinase 2 controls insulin secretion and glucose homeostasis.Nature chemical biology · 2024Article
- LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells.Cell reports · 2024Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding.Nature communications · 2024Article
- Exploring potential targets for natural product therapy of DN: the role of SUMOylation.Frontiers in pharmacology · 2024Review
- Stem Cell Therapy for the Management of Type 1 Diabetes: Advances and Perspectives.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 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
- Sardinian Infants of Diabetic Mothers: A Metabolomics Observational Study.International journal of molecular sciences · 2023Observational
- Lactate: an intracellular metabolite regulates cell cycle progression.Life metabolism · 2023Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 9 institutions in 5 countries.
Funding
Abstract
Insulin secretion from β cells of the pancreatic islets of Langerhans controls metabolic homeostasis and is impaired in individuals with type 2 diabetes (T2D). Increases in blood glucose trigger insulin release by closing ATP-sensitive K+ channels, depolarizing β cells, and opening voltage-dependent Ca2+ channels to elicit insulin exocytosis. However, one or more additional pathway(s) amplify the secretory response, likely at the distal exocytotic site. The mitochondrial export of isocitrate and engagement with cytosolic isocitrate dehydrogenase (ICDc) may be one key pathway, but the mechanism linking this to insulin secretion and its role in T2D have not been defined. Here, we show that the ICDc-dependent generation of NADPH and subsequent glutathione (GSH) reduction contribute to the amplification of insulin exocytosis via sentrin/SUMO-specific protease-1 (SENP1). In human T2D and an in vitro model of human islet dysfunction, the glucose-dependent amplification of exocytosis was impaired and could be rescued by introduction of signaling intermediates from this pathway. Moreover, islet-specific Senp1 deletion in mice caused impaired glucose tolerance by reducing the amplification of insulin exocytosis. Together, our results identify a pathway that links glucose metabolism to the amplification of insulin secretion and demonstrate that restoration of this axis rescues β cell function in T2D.
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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.