ArticleAging2019
The role of ORMDL3/ATF6 in compensated beta cell proliferation during early diabetes.
Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes.Journal of internal medicine · 2021Pooled it
- Deletion of the T1D risk geneBiochemistry and biophysics reports · 2026Article
- ORMDL3 as Key Regulator of Endothelial Dysfunction in Atherosclerosis via Sphingolipid Biosynthesis.Inflammation · 2026Article
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Orm2 promotes nitrogen-induced sphingolipid production and endocytosis via Orm1 phosphorylation.Journal of lipid research · 2025Article
- METTL3 overexpression and ATF6 silencing-induced Inhibition in HAS2 expression relieves PDGF-BB stimulation-induced HA production and the proliferation of human orbital fibroblasts in graves' ophthalmopathy.Journal of endocrinological investigation · 2025Article
- Simultaneous deletion of ORMDL1 and ORMDL3 proteins disrupts immune cell homeostasis.Frontiers in immunology · 2024Article
- In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR.Nature metabolism · 2021Article
- Intersection of the ATF6 and XBP1 ER stress pathways in mouse islet cells.The Journal of biological chemistry · 2020Article
- Differential Expression of Ormdl Genes in the Islets of Mice and Humans with Obesity.iScience · 2020Article
- ORMDL3 and Asthma: Linking Sphingolipid Regulation to Altered T Cell Function.Frontiers in immunology · 2020Review
- The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic Rats.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Arthropods Under Pressure: Stress Responses and Immunity at the Pathogen-Vector Interface.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress in beta cells induces a signaling network called the unfolded protein response (UPR), which plays a dual role in diabetes. A key regulator of ER-stress and UPR, the orosomucoid 1-like protein 3 (ORMDL3), has been shown to regulate airway remodeling through a major UPR protein, activating transcription factor 6 (ATF6), but the contribution of this regulatory axis to compensatory pancreatic beta cell proliferation in diabetes has not been studied. Here, we detected significantly lower levels of ORMDL3 mRNA in leukocytes of peripheral blood specimens from type 1 diabetes (T1D) children, compared to normal children. Moreover, these ORMDL3 levels in T1D children exhibited further decreases upon follow-up. ORMDL3 levels in islets from NOD mice, a mouse model for T1D in humans, showed a mild increase before diabetes onset, but a gradual decrease subsequently. In high glucose culture, beta cell proliferation, but not apoptosis, was increased by overexpression of ORMDL3 levels, likely mediated by its downstream factor ATF6. Mechanistically, ORMDL3 transcriptionally activated ATF6, which was confirmed in a promoter reporter assay. Together, our data suggest that ORMDL3 may increase beta cell proliferation through ATF6 as an early compensatory change in response to diabetes.
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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.