ArticleMolecular endocrinology (Baltimore, Md.)2014
Multiparameter screening reveals a role for Na+ channels in cytokine-induced β-cell death.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Sodium channels in non-excitable cells: powerful actions and therapeutic targets beyond Hodgkin and Huxley.Trends in cell biology · 2025Review
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Differential Effects of Voclosporin and Tacrolimus on Insulin Secretion From Human Islets.Endocrinology · 2020Article
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Oestrogen receptor β mediates the actions of bisphenol-A on ion channel expression in mouse pancreatic beta cells.Diabetologia · 2019Article
- A novel inhibitor of inducible NOS dimerization protects against cytokine-induced rat beta cell dysfunction.British journal of pharmacology · 2018Article
- Epithelial Sodium Channel in Aldosterone-Induced Endothelium Stiffness and Aortic Dysfunction.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Carbamazepine, a beta-cell protecting drug, reduces type 1 diabetes incidence in NOD mice.Scientific reports · 2018Article
- Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy.International journal of molecular sciences · 2016Review
- High-content screening identifies a role for Na(+) channels in insulin production.Royal Society open science · 2015Article
- Temporal Heterogeneity Metrics in Apoptosis Induced by Anticancer Drugs.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2015Article
- Article
- A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in mouse primary beta cells.Diabetologia · 2015Article
- A practical guide to genetic engineering of pancreatic β-cells in vivo: getting a grip on RIP and MIP.Islets · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic β-cell death plays a role in both type 1 and type 2 diabetes, but clinical treatments that specifically target β-cell survival have not yet been developed. We have recently developed live-cell imaging-based, high-throughput screening methods capable of identifying factors that modulate pancreatic β-cell death, with the hope of finding drugs that can intervene in this process. In the present study, we used a high-content screen and the Prestwick Chemical Library of small molecules to identify drugs that block cell death resulting from exposure to a cocktail of cytotoxic cytokines (25 ng/mL TNF-α, 10 ng/mL IL-1β, and 10 ng/mL IFN-γ). Data analysis with self-organizing maps revealed that 19 drugs had profiles similar to that of the no cytokine condition, indicating protection. Carbamazepine, an antiepileptic Na(+) channel inhibitor, was particularly interesting because Na(+) channels are not generally considered targets for antiapoptotic therapy in diabetes and because the function of these channels in β-cells has not been well studied. We analyzed the expression and characteristics of Na(+) currents in mature β-cells from MIP-GFP mice. We confirmed the dose-dependent protective effects of carbamazepine and another use-dependent Na(+) channel blocker in cytokine-treated mouse islet cells. Carbamazepine down-regulated the proapoptotic and endoplasmic reticulum stress signaling induced by cytokines. Together, these studies point to Na(+) channels as a novel therapeutic target in diabetes.
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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 Socratic graph.