ArticleThe EMBO journal1997
Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 180 citations in OpenAlex.
- GPR180 deficiency impairs mitochondrial function and insulin secretion in pancreatic β-cells.Molecular metabolism · 2026Article
- Mitochondrial calcium modulates odor-mediated behavioral plasticity in Caenorhabditis elegans.Molecules and cells · 2026Article
- Article
- Three-dimensional bioprinting of functional β-islet-like constructs.International journal of bioprinting · 2023Article
- Metabolism-secretion coupling in glucose-stimulated insulin secretion.Diabetology international · 2022Review
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response.Nature communications · 2021Article
- Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress.Biomolecules · 2020Article
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?Endocrine reviews · 2020Review
- The Loss of ARNT/HIF1β in Male Pancreatic β-Cells Is Protective Against High-Fat Diet-Induced Diabetes.Endocrinology · 2019Article
- Glutamate as intracellular and extracellular signals in pancreatic islet functions.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- Mitochondrially derived peptides as novel regulators of metabolism.The Journal of physiology · 2017Review
- The Mitochondrial Voltage-Dependent Anion Channel 1, CaFrontiers in oncology · 2017Review
- Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity.Cell death & disease · 2015Article
- Dual Monitoring of Secretion and ATP Levels during Chondrogenesis Using Perfusion Culture-Combined Bioluminescence Monitoring System.BioMed research international · 2015Article
- Article
- Mathematical models of electrical activity of the pancreatic β-cell: a physiological review.Islets · 2014Review
- Glucose-stimulated insulin secretion: A newer perspective.Journal of diabetes investigation · 2013Review
- A role for cytosolic isocitrate dehydrogenase as a negative regulator of glucose signaling for insulin secretion in pancreatic ß-cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the pancreatic beta-cell, insulin secretion is stimulated by glucose metabolism resulting in membrane potential-dependent elevation of cytosolic Ca2+ ([Ca2+]c). This cascade involves the mitochondrial membrane potential (delta psi[m]) hyperpolarization and elevation of mitochondrial Ca2+ ([Ca2+]m) which activates the Ca(2+)-sensitive NADH-generating dehydrogenases. Metabolism-secretion coupling requires unidentified signals, other than [Ca2+]c, possibly generated by the mitochondria through the rise in [Ca2+]m. To test this paradigm, we have established an alpha-toxin permeabilized cell preparation permitting the simultaneous monitoring of [Ca2+] with mitochondrially targeted aequorin and insulin secretion under conditions of saturating [ATP] (10 mM) and of clamped [Ca2+]c at substimulatory levels (500 nM). The tricarboxylic acid (TCA) cycle intermediate succinate hyperpolarized delta psi(m), raised [Ca2+]m up to 1.5 microM and stimulated insulin secretion 20-fold, without changing [Ca2+]c. Blockade of the uniporter-mediated Ca2+ influx into the mitochondria abolished the secretory response. Moreover, glycerophosphate, which raises [Ca2+]m by hyperpolarizing delta psi(m) without supplying carbons to the TCA cycle, failed to stimulate exocytosis. Activation of the TCA cycle with citrate evoked secretion only when combined with glycerophosphate. Thus, mitochondrially driven insulin secretion at permissive [Ca2+]c requires both a substrate for the TCA cycle and a rise in [Ca2+]m. Therefore, mitochondrial metabolism generates factors distinct from Ca2+ and ATP capable of inducing insulin exocytosis.
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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.