ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
PDIA6 regulates insulin secretion by selectively inhibiting the RIDD activity of IRE1.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 73 citations in OpenAlex.
- Quantitative interactome mapping of skeletal muscle insulin resistance.Molecular systems biology · 2026Article
- Single-nuclei UPR profiling by flow cytometry reveals bortezomib resistance mechanisms in multiple myeloma.EMBO molecular medicine · 2026Article
- Protein Disulfide Isomerase A6 (PDIA6) Restrains Heat-Induced Oxidative Damage in Haemocytes of the Pacific Oyster (Antioxidants (Basel, Switzerland) · 2026Article
- Lipid Metabolic Disorders: a Pivotal Driver in Type 2 Diabetes Mellitus Pathogenesis.Current obesity reports · 2026Review
- Polyadenylation of insulin mRNA by Tent5a regulates pancreatic beta cells.Nature communications · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- CaNature cell biology · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Development of an Endoplasmic Reticulum Stress-Related Diagnostic Signature in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- The IRE1β-mediated unfolded protein response is repressed by the chaperone AGR2 in mucin producing cells.The EMBO journal · 2024Article
- Activation of goblet-cell stress sensor IRE1β is controlled by the mucin chaperone AGR2.The EMBO journal · 2024Article
- Increased cellular protein modification by methylglyoxal activates endoplasmic reticulum-based sensors of the unfolded protein response.Redox biology · 2024Article
- Physiological ER stress caused by amylase production induces regulated Ire1-dependent mRNA decay in Aspergillus oryzae.Communications biology · 2023Article
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- Myogenesis in C2C12 Cells Requires Phosphorylation of ATF6α by p38 MAPK.Biomedicines · 2023Article
- Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model.Blood advances · 2023Article
- Unfolding the Interactions between Endoplasmic Reticulum Stress and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Vx-809, a CFTR Corrector, Acts through a General Mechanism of Protein Folding and on the Inflammatory Process.International journal of molecular sciences · 2023Article
- A biallelic loss-of-function PDIA6 variant in a second patient with polycystic kidney disease, infancy-onset diabetes, and microcephaly.Clinical genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling. In this study, shRNA silencing of PDIA6 expression in insulin-producing mouse cells reduced insulin production (5-fold) and, consequently, glucose-stimulated insulin secretion (3-4-fold). This inhibition of insulin release was independent of the PDIA6-PERK interaction or PERK activity. Acute inhibition of PERK did not change the short-term response of β cells to glucose. Rather, PDIA6 affected insulin secretion by modulating one of the activities of IRE1. At 11 mM glucose and lower, the regulated IRE1-dependent decay (RIDD) of the mRNA activity of IRE1 was activated, but not its X-box binding protein (XBP)-1 splicing activity. In the absence of PDIA6, RIDD activity toward insulin transcripts was enhanced up to 4-fold, as shown by molecular assays in cultured cells and the use of a fluorescent reporter in intact islets. Such physiologic activation of IRE1 by glucose contrasted with IRE1 activation by chemical stress, when both IRE1 activities were induced. Thus, whereas the stimulus determines the quality of IRE1 signaling, PDIA6 attenuates multiple enzymatic activities of IRE1, maintaining its signaling within a physiologically tolerable range.
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.