ArticleDiabetes2016
Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 67 citations in OpenAlex.
- Dapansutrile preserves pancreatic beta-cell function by regulating insulin vesicle membrane fusion and mitochondrial homeostasis.Diabetes, obesity & metabolism · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Single Fusion Pore Analysis via Single Cell Amperometry Uncovers Impaired Pore Expansion That Restricts Insulin Exocytosis in Human Type 2 Diabetes.Angewandte Chemie (International ed. in English) · 2025Article
- Fusion Pores as Regulators of Quantal Size and Cellular Physiology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.Biophysical journal · 2025Article
- Diagnostic Roles of circXPNPEP3 as Biomarker for Diabetic Nephropathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Identification of genes related to fatty acid metabolism in type 2 diabetes mellitus.Biochemistry and biophysics reports · 2024Article
- Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.bioRxiv : the preprint server for biology · 2024Article
- Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.Cell metabolism · 2024Article
- LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis.Journal of diabetes · 2024Article
- SOXC are critical regulators of adult bone mass.Nature communications · 2024Article
- Three membrane fusion pore families determine the pathway to pore dilation.Biophysical journal · 2023Article
- High-speed imaging reveals the bimodal nature of dense core vesicle exocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterization of Two MouseInternational journal of molecular sciences · 2022Article
- Inhibition of the lncRNAMolecular therapy. Nucleic acids · 2022Article
- Incorporating regulatory interactions into gene-set analyses for GWAS data: A controlled analysis with the MAGMA tool.PLoS computational biology · 2022Article
- SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway.Open life sciences · 2022Article
- Dynamin deficiency causes insulin secretion failure and hyperglycemia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores.eLife · 2021Article
- Behavioral and Gene Expression Analysis of Stxbp6-Knockout Mice.Brain sciences · 2021Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The transcription factor Sox4 has been proposed to underlie the increased type 2 diabetes risk linked to an intronic single nucleotide polymorphism in CDKAL1 In a mouse model expressing a mutant form of Sox4, glucose-induced insulin secretion is reduced by 40% despite normal intracellular Ca(2+) signaling and depolarization-evoked exocytosis. This paradox is explained by a fourfold increase in kiss-and-run exocytosis (as determined by single-granule exocytosis measurements) in which the fusion pore connecting the granule lumen to the exterior expands to a diameter of only 2 nm, which does not allow the exit of insulin. Microarray analysis indicated that this correlated with an increased expression of the exocytosis-regulating protein Stxbp6. In a large collection of human islet preparations (n = 63), STXBP6 expression and glucose-induced insulin secretion correlated positively and negatively with SOX4 expression, respectively. Overexpression of SOX4 in the human insulin-secreting cell EndoC-βH2 interfered with granule emptying and inhibited hormone release, the latter effect reversed by silencing STXBP6 These data suggest that increased SOX4 expression inhibits insulin secretion and increased diabetes risk by the upregulation of STXBP6 and an increase in kiss-and-run exocytosis at the expense of full fusion. We propose that pharmacological interventions promoting fusion pore expansion may be effective in diabetes therapy.
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.