ArticleThe Journal of biological chemistry2013
Carbamazepine as a novel small molecule corrector of trafficking-impaired ATP-sensitive potassium channels identified in congenital hyperinsulinism.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Identification and rescue of congenital hyperinsulinism-associated ABCC8 mutations that impair KThe Journal of biological chemistry · 2025Article
- Article
- ClC-1 Chloride Channel: Inputs on the Structure-Function Relationship of Myotonia Congenita-Causing Mutations.Biomedicines · 2023Review
- Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives.Nutrients · 2023Review
- Personalized Therapeutics for KAnnual review of pharmacology and toxicology · 2023Review
- Mechanistic insights on KATP channel regulation from cryo-EM structures.The Journal of general physiology · 2023Review
- KFrontiers in endocrinology · 2023Review
- Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism.Frontiers in endocrinology · 2023Article
- Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated NaInternational journal of molecular sciences · 2022Article
- Carbamazepine promotes surface expression of mutant Kir6.2-A28V ATP-sensitive potassium channels by modulating Golgi retention and autophagy.The Journal of biological chemistry · 2022Article
- Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes.Nature communications · 2022Article
- Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.Methods in enzymology · 2021Article
- Kir Channel Molecular Physiology, Pharmacology, and Therapeutic Implications.Handbook of experimental pharmacology · 2021Review
- Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.Reviews in endocrine & metabolic disorders · 2020Review
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Pharmacological chaperones of ATP-sensitive potassium channels: Mechanistic insight from cryoEM structures.Molecular and cellular endocrinology · 2020Review
- Novel dominant KAmerican journal of medical genetics. Part A · 2019Article
- Article
- Functional characterization of activating mutations in the sulfonylurea receptor 1 (ABCC8) causing neonatal diabetes mellitus in Asian Indian children.Pediatric diabetes · 2019Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
ATP-sensitive potassium (KATP) channels consisting of sulfonylurea receptor 1 (SUR1) and the potassium channel Kir6.2 play a key role in insulin secretion by coupling metabolic signals to β-cell membrane potential. Mutations in SUR1 and Kir6.2 that impair channel trafficking to the cell surface lead to loss of channel function and congenital hyperinsulinism. We report that carbamazepine, an anticonvulsant, corrects the trafficking defects of mutant KATP channels previously identified in congenital hyperinsulinism. Strikingly, of the 19 SUR1 mutations examined, only those located in the first transmembrane domain of SUR1 responded to the drug. We show that unlike that reported for several other protein misfolding diseases, carbamazepine did not correct KATP channel trafficking defects by activating autophagy; rather, it directly improved the biogenesis efficiency of mutant channels along the secretory pathway. In addition to its effect on channel trafficking, carbamazepine also inhibited KATP channel activity. Upon subsequent removal of carbamazepine, however, the function of rescued channels was recovered. Importantly, combination of the KATP channel opener diazoxide and carbamazepine led to enhanced mutant channel function without carbamazepine washout. The corrector effect of carbamazepine on mutant KATP channels was also demonstrated in rat and human β-cells with an accompanying increase in channel activity. Our findings identify carbamazepine as a novel small molecule corrector that may be used to restore KATP channel expression and function in a subset of congenital hyperinsulinism patients.
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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.