ArticleProceedings of the National Academy of Sciences of the United States of America2013
Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- pH-dependent activation of the NaNature communications · 2026Article
- Trafficking of the human NaProtein science : a publication of the Protein Society · 2026Article
- Structure and Inhibition of the Human NaInternational journal of molecular sciences · 2025Article
- PIPNature communications · 2025Article
- Residues R177 and S178 of the human NaFEBS letters · 2025Article
- Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.Molecular neurobiology · 2024Review
- The crossing of two unwound transmembrane regions that is the hallmark of the NhaA structural fold is critical for antiporter activity.Scientific reports · 2024Article
- NaInternational journal of molecular sciences · 2023Review
- Allosteric links between the hydrophilic N-terminus and transmembrane core of human NaProtein science : a publication of the Protein Society · 2022Article
- The Physiological Function and Potential Role of the Ubiquitous NaInternational journal of molecular sciences · 2022Review
- Prokaryotic NaInternational journal of molecular sciences · 2022Review
- Association between host genetics of sheep and the rumen microbial composition.Tropical animal health and production · 2022Article
- Structure, mechanism and lipid-mediated remodeling of the mammalian NaNature structural & molecular biology · 2022Article
- The Less Well-Known Little Brothers: The SLC9B/NHA Sodium Proton Exchanger Subfamily-Structure, Function, Regulation and Potential Drug-Target Approaches.Frontiers in physiology · 2022Review
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Susceptibility to Metabolic Diseases in COVID-19: To be or Not to be an Issue.Frontiers in molecular biosciences · 2022Review
- Dynamin deficiency causes insulin secretion failure and hyperglycemia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Insight into the direct interaction of NaScientific reports · 2021Article
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NHA2 is a sodium/hydrogen exchanger with unknown physiological function. Here we show that NHA2 is present in rodent and human β-cells, as well as β-cell lines. In vivo, two different strains of NHA2-deficient mice displayed a pathological glucose tolerance with impaired insulin secretion but normal peripheral insulin sensitivity. In vitro, islets of NHA2-deficient and heterozygous mice, NHA2-depleted Min6 cells, or islets treated with an NHA2 inhibitor exhibited reduced sulfonylurea- and secretagogue-induced insulin secretion. The secretory deficit could be rescued by overexpression of a wild-type, but not a functionally dead, NHA2 transporter. NHA2 deficiency did not affect insulin synthesis or maturation and had no impact on basal or glucose-induced intracellular Ca(2+) homeostasis in islets. Subcellular fractionation and imaging studies demonstrated that NHA2 resides in transferrin-positive endosomes and synaptic-like microvesicles but not in insulin-containing large dense core vesicles in β-cells. Loss of NHA2 inhibited clathrin-dependent, but not clathrin-independent, endocytosis in Min6 and primary β-cells, suggesting defective endo-exocytosis coupling as the underlying mechanism for the secretory deficit. Collectively, our in vitro and in vivo studies reveal the sodium/proton exchanger NHA2 as a critical player for insulin secretion in the β-cell. In addition, our study sheds light on the biological function of a member of this recently cloned family of transporters.
Indexed as
Identifiers
What OpenQuestion holds
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.