ArticleBMC medicine2014
CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin secretion in human and murine pancreatic beta-cells.
Article in BMC medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04379726 (Characterization of β-cell Function and Insulin Sensitivity in Pre-transplant Patients With Cystic Fibrosis), which is not on this map. Cited by 85 papers.
What it found
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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.
Characterization of β-cell Function and Insulin Sensitivity in Pre-transplant Patients With Cystic Fibrosis
Who cites it
85 citing papers in PubMed, 134 citations in OpenAlex.
- Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.Diabetes · 2022Trial
- MicroRNA-Driven Regulation of β-Cell Function in Type 2 Diabetes: Molecular Mechanisms, Network Insights, and Translational Perspectives.Acta physiologica (Oxford, England) · 2026Review
- Unravelling the developmental origins of cystic fibrosis-related diabetes.Diabetologia · 2026Review
- Isolated Hypoglycemia in Children with Cystic Fibrosis: Role of Pancreatic Insufficiency and Glucagon ResponseJournal of clinical research in pediatric endocrinology · 2026Article
- Article
- The endocrine complications of cystic fibrosis.Nature reviews. Endocrinology · 2026Review
- Elexacaftor-tezacaftor-ivacaftor enhances first-phase insulin secretion and improves glucose control in cystic fibrosis.Endocrine connections · 2026Article
- Post-marketing safety profile of lumacaftor/ivacaftor in cystic fibrosis treatment: a pharmacovigilance analysis based on FAERS.Frontiers in medicine · 2026Article
- From Pathophysiology to Treatment: Contemporary Approaches to CFRD in the Pediatric and Adolescent Population.Pediatric diabetes · 2026Review
- Hitting the Sweet Spot: The Impact of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Cystic Fibrosis.American journal of respiratory and critical care medicine · 2025Article
- Glucagon-like peptide-1 receptor agonists in adults with cystic fibrosis-related diabetes: Rationale and emerging evidence.Diabetes, obesity & metabolism · 2025Article
- Glycemia and Insulin Secretion in Cystic Fibrosis 2 Years After Elexacaftor/Tezacaftor/Ivacaftor: PROMISE-ENDO.The Journal of clinical endocrinology and metabolism · 2025Observational
- Eukaryotic translation initiation factor 2A protects pancreatic beta cells during endoplasmic reticulum stress while rescuing global translation inhibition.Diabetologia · 2025Article
- Prevalence and Characteristics of Patients with Cystic Fibrosis-Related Diabetes in Croatia.Life (Basel, Switzerland) · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Genome Sequencing Reveals the Adaptation of Chickens to High Altitudes in Different Regions.Animals : an open access journal from MDPI · 2025Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes.Diabetes · 2023Review
- Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes.Diabetes care · 2023Review
- Hypoglycaemia after Initiation of CFTR Modulator Therapy in a Cystic Fibrosis Patient without Diabetes.Case reports in endocrinology · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene lead to the disease cystic fibrosis (CF). Although patients with CF often have disturbances in glucose metabolism including impaired insulin release, no previous studies have tested the hypothesis that CFTR has a biological function in pancreatic beta-cells.
methodsExperiments were performed on islets and single beta-cells from human donors and NMRI-mice. Detection of CFTR was investigated using PCR and confocal microscopy. Effects on insulin secretion were measured with radioimmunoassay (RIA). The patch-clamp technique was used to measure ion channel currents and calcium-dependent exocytosis (as changes in membrane capacitance) on single cells with high temporal resolution. Analysis of ultrastructure was done on transmission electron microscopy (TEM) images.
resultsWe detected the presence of CFTR and measured a small CFTR conductance in both human and mouse beta-cells. The augmentation of insulin secretion at 16.7 mM glucose by activation of CFTR by cAMP (forskolin (FSK) or GLP-1) was significantly inhibited when CFTR antagonists (GlyH-101 and/or CFTRinh-172) were added. Likewise, capacitance measurements demonstrated reduced cAMP-dependent exocytosis upon CFTR-inhibition, concomitant with a decreased number of docked insulin granules. Finally, our studies demonstrate that CFTR act upstream of the chloride channel Anoctamin 1 (ANO1; TMEM16A) in the regulation of cAMP- and glucose-stimulated insulin secretion.
conclusionOur work demonstrates a novel function for CFTR as a regulator of pancreatic beta-cell insulin secretion and exocytosis, and put forward a role for CFTR as regulator of ANO1 and downstream priming of insulin granules prior to fusion and release of insulin. The pronounced regulatory effect of CFTR on insulin secretion is consistent with impaired insulin secretion in patients with CF.
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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.