ArticleProceedings of the National Academy of Sciences of the United States of America2014
Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases.Frontiers in immunology · 2025Review
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Integrating genome-wide association studies and population genomics analysis reveals the genetic architecture of growth and backfat traits in pigs.Frontiers in genetics · 2022Article
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects.Nature communications · 2021Article
- The Calcium-Activated Chloride Channel TMEM16A is Inhibitied by Liquiritigenin.Frontiers in pharmacology · 2021Article
- Hepatocyte TMEM16A Deletion Retards NAFLD Progression by Ameliorating Hepatic Glucose Metabolic Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Chloride transporters and channels in β-cell physiology: revisiting a 40-year-old model.Biochemical Society transactions · 2019Review
- An Exploratory Association Analysis of the Insulin Gene Region With Diabetes Mellitus in Two Dog Breeds.The Journal of heredity · 2019Article
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- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- 4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities.Scientific reports · 2017Article
- Anoctamin 1 (Ano1) is required for glucose-induced membrane potential oscillations and insulin secretion by murine β-cells.Pflugers Archiv : European journal of physiology · 2016Article
- βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.Genes & development · 2016Article
- Cellular functions of TMEM16/anoctamin.Pflugers Archiv : European journal of physiology · 2016Review
- Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function.Current diabetes reports · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We used circular chromatin conformation capture (4C) to identify a physical contact in human pancreatic islets between the region near the insulin (INS) promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, which encodes a Ca(2+)-dependent chloride ion channel. In response to glucose, this contact was strengthened and ANO1 expression increased, whereas inhibition of INS gene transcription by INS promoter targeting siRNA decreased ANO1 expression, revealing a regulatory effect of INS promoter on ANO1 expression. Knockdown of ANO1 expression caused decreased insulin secretion in human islets, establishing a physical proximity-dependent feedback loop involving INS transcription, ANO1 expression, and insulin secretion. To explore a possible role of ANO1 in insulin metabolism, we carried out experiments in Ano1(+/-) mice. We observed reduced serum insulin levels and insulin-to-glucose ratios in high-fat diet-fed Ano1(+/-) mice relative to Ano1(+/+) mice fed the same diet. Our results show that determination of long-range contacts within the nucleus can be used to detect novel and physiologically relevant mechanisms. They also show that networks of long-range physical contacts are important to the regulation of insulin metabolism.
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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.