ArticleEndocrinology2008
Endoplasmic reticulum stress-induced activation of activating transcription factor 6 decreases insulin gene expression via up-regulation of orphan nuclear receptor small heterodimer partner.
Article in Endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels.Arteriosclerosis, thrombosis, and vascular biology · 2009Pooled it
- Stimulation to secrete insulin induces pancreatic β-cell dysfunction through Tfe3 activation.iScience · 2026Article
- Structural Characterization of Protein-Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods.International journal of molecular sciences · 2025Review
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- The rs2341471-G/G genotype of activating transcription factor 6 (ATF6) is the risk factor of type 2 diabetes in subjects with obesity or overweight.International journal of obesity (2005) · 2024Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
- Tangeretin enhances pancreatic beta-TC-6 function by ameliorating tunicamycin-induced cellular perturbations.Molecular biology reports · 2023Article
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- FK506-Binding Protein 2 Participates in Proinsulin Folding.Biomolecules · 2023Article
- Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes.bioRxiv : the preprint server for biology · 2023Article
- Wolfram Syndrome 1: From Genetics to Therapy.International journal of environmental research and public health · 2022Review
- Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells.Frontiers in endocrinology · 2022Review
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Living Dangerously: Protective and Harmful ER Stress Responses in Pancreatic β-Cells.Diabetes · 2021Review
- Small heterodimer partner (SHP) aggravates ER stress in Parkinson's disease-linked LRRK2 mutant astrocyte by regulating XBP1 SUMOylation.Journal of biomedical science · 2021Article
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Wolfram syndrome 1 gene regulates pathways maintaining beta-cell health and survival.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Mechanisms of impaired pancreatic β‑cell function in high‑fat diet‑induced obese mice: The role of endoplasmic reticulum stress.Molecular medicine reports · 2020Article
- Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in PancreaticJournal of diabetes research · 2020Review
- Wolfram syndrome, a rare neurodegenerative disease: from pathogenesis to future treatment perspectives.Journal of translational medicine · 2019Review
5 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
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The highly developed endoplasmic reticulum (ER) structure of pancreatic beta-cells is a key factor in beta-cell function. Here we examined whether ER stress-induced activation of activating transcription factor (ATF)-6 impairs insulin gene expression via up-regulation of the orphan nuclear receptor small heterodimer partner (SHP; NR0B2), which has been shown to play a role in beta-cell dysfunction. We examined whether ER stress decreases insulin gene expression, and this process is mediated by ATF6. A small interfering RNA that targeted SHP was used to determine whether the effect of ATF6 on insulin gene expression is mediated by SHP. We also measured the expression level of ATF6 in pancreatic islets in Otsuka Long Evans Tokushima Fatty rats, a rodent model of type 2 diabetes. High glucose concentration (30 mmol/liter glucose) increased ER stress in INS-1 cells. ER stress induced by tunicamycin, thapsigargin, or dithiotreitol decreased insulin gene transcription. ATF6 inhibited insulin promoter activity, whereas X-box binding protein-1 and ATF4 did not. Adenovirus-mediated overexpression of active form of ATF6 in INS-1 cells impaired insulin gene expression and secretion. ATF6 also down-regulated pancreatic duodenal homeobox factor-1 and RIPE3b1/MafA gene expression and repressed the cooperative action of pancreatic duodenal homeobox factor-1, RIPE3b1/MafA, and beta-cell E box transactivator 2 in stimulating insulin transcription. The ATF6-induced suppression of insulin gene expression was associated with up-regulation of SHP gene expression. Finally, we found that expression of ATF6 was increased in the pancreatic islets of diabetic Otsuka Long Evans Tokushima Fatty rats, compared with their lean, nondiabetic counterparts, Long-Evans Tokushima Otsuka rats. Collectively, this study shows that ER stress-induced activation of ATF6 plays an important role in the development of beta-cell dysfunction.
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.