ArticleThe journal of physiological sciences : JPS2014
Chronic exposure to valproic acid promotes insulin release, reduces KATP channel current and does not affect Ca (2+) signaling in mouse islets.
Article in The journal of physiological sciences : JPS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses.Neurochemical research · 2025Review
- Effects of Valproate on Intracellular Calcium Ion Signaling: Implications for Mechanistic Research.Psychopharmacology bulletin · 2025Article
- Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis.Frontiers in endocrinology · 2021Review
- Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.International journal of molecular sciences · 2020Review
- Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells.The journal of physiological sciences : JPS · 2019Article
- SIRT5 regulates pancreatic β-cell proliferation and insulin secretion in type 2 diabetes.Experimental and therapeutic medicine · 2018Article
- Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperinsulinemia is one of the reported side effects of valproic acid (VPA), a medicine used to treat epilepsy. However, its underlying mechanism remains unknown. The present study was designed to investigate a direct effect of VPA on insulin secretion by using mouse pancreactic islets and β-cells. VPA had no acute effect on insulin secretion from islets, or on cytosolic Ca(2+) ([Ca(2+)]i) in single β-cells. However, following long-term exposure to VPA (48 h), both basal and glucose-stimulated insulin secretion were markedly elevated (5-fold), while the insulin gene expression level was unaltered. Following long-term exposure to VPA, β-cells showed a decrease in whole cell KATP channel current. However, the increase in [Ca(2+)]i in response to the sulfonylurea drug, tolbutamide was attenuated. The present study shows that VPA has no acute effects, but long-term treatment results in enhancement of both basal and glucose-stimulated insulin secretion. This long-term effect may mediate the KATP channel, while VPA can also attenuate the effect of the KATP channel blocker tolbutamide.
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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.