ArticlePLoS biology2009
Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation.
Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
190 citing papers in PubMed, 1 synthesis or guideline pooled it, 381 citations in OpenAlex.
- The effect of selective serotonin re-uptake inhibitors on risk of type II diabetes mellitus and acute pancreatitis: a meta-analysis.Bioscience reports · 2018Pooled it
- GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cyclic stretch increases transglutaminase 2-mediated serotonylation of extracellular fibronectin in cultured optic nerve head astrocytes: a pilot study.Matrix biology plus · 2026Article
- Profiles of FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in GEP-NETs: A Comparative Tumor-Margin Study Based on Protein Concentration.International journal of molecular sciences · 2026Article
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Monoaminylation in Human Health and Disease: State of the Field, Challenges, and Emerging Directions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Special Issue "Serotonin in Health and Diseases".International journal of molecular sciences · 2026Article
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- The Acari Hypothesis, VIII: the human apocrine-mammary-microbiota axis andFrontiers in microbiology · 2026Article
- Vortioxetine enhances the anti-pancreatic cancer efficacy of gemcitabine through reducing MAOB expression.Frontiers in pharmacology · 2026Article
- Effect of a Combined Antidepressant Drug Flupentixol-Melitracen on Glucose Level and Expression of Insulin-Like Peptide Genes DILP5 and DILP6 in Drosophila melanogaster.BioMed research international · 2026Article
- The gut feeling in motion sickness.Communications biology · 2025Review
- The Impact of Gut Microbial Metabolomics on Type 2 Diabetes Development in People Living with HIV.Metabolites · 2025Review
- Review
- Role of Serotonin on Gene Expression and Physiology in Human Cytotrophoblasts and Placenta.Endocrinology · 2025Article
- Dietary and Nutritional Strategies to Prevent Uremic Toxin Formation and Slow the Progression of Diabetic Kidney Disease.Journal of clinical medicine · 2025Review
- Horizontal and longitudinal targeted metabolomics in healthy pregnancy and gestational diabetes mellitus.Acta diabetologica · 2025Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While serotonin (5-HT) co-localization with insulin in granules of pancreatic beta-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is still unclear. We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion. We found that these mice are diabetic and have an impaired insulin secretion due to the lack of 5-HT in the pancreas. The pharmacological restoration of peripheral 5-HT levels rescued the impaired insulin secretion in vivo. These findings were further evidenced by patch clamp experiments with isolated Tph1-/- beta-cells, which clearly showed that the secretory defect is downstream of Ca(2+)-signaling and can be rescued by direct intracellular application of 5-HT via the clamp pipette. In elucidating the underlying mechanism further, we demonstrate the covalent coupling of 5-HT by transglutaminases during insulin exocytosis to two key players in insulin secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively active in a receptor-independent signaling mechanism we have recently termed serotonylation. Concordantly, an inhibition of such activating serotonylation in beta-cells abates insulin secretion. We also observed inactivation of serotonylated Rab3a by enhanced proteasomal degradation, which is in line with the inactivation of other serotonylated GTPases. Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic beta-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.
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What Socratic holds
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 Socratic graph.