ArticleDiabetologia2006
Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells.
Article in Diabetologia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Tumor necrosis factor-α promotes abnormal glucose metabolism after acute pancreatitis by inducing islet β-cell apoptosisWorld journal of gastroenterology · 2025Article
- Growth arrest and DNA damage-inducible 45: a new player on inflammatory diseases.Frontiers in immunology · 2025Review
- Expression of Human Mutant Preproinsulins Induced Unfolded Protein Response,International journal of molecular sciences · 2021Article
- Hepatic Gadd45β promotes hyperglycemia and glucose intolerance through DNA demethylation of PGC-1α.The Journal of experimental medicine · 2021Article
- GADD45B Promotes Glucose-Induced Renal Tubular Epithelial-Mesenchymal Transition and ApoptosisFrontiers in physiology · 2020Article
- Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.Biomedicines · 2017Review
- Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation.The Journal of pharmacology and experimental therapeutics · 2016Article
- GADD45B mediates podocyte injury in zebrafish by activating the ROS-GADD45B-p38 pathway.Cell death & disease · 2016Article
- Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4.Cell death & disease · 2016Article
- Gadd45b is a novel mediator of neuronal apoptosis in ischemic stroke.International journal of biological sciences · 2015Article
- GADD45β mediates p53 protein degradation via Src/PP2A/MDM2 pathway upon arsenite treatment.Cell death & disease · 2013Article
- Prunella vulgaris aqueous extract attenuates IL-1β-induced apoptosis and NF-κB activation in INS-1 cells.Experimental and therapeutic medicine · 2012Article
- Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis.European cells & materials · 2011Article
- Expression profiling after activation of amino acid deprivation response in HepG2 human hepatoma cells.Physiological genomics · 2010Article
- Gadd45 proteins as critical signal transducers linking NF-kappaB to MAPK cascades.Current cancer drug targets · 2009Review
- Gadd45beta deficiency in rheumatoid arthritis: enhanced synovitis through JNK signaling.Arthritis and rheumatism · 2009Article
- Possible regulation of genes associated with intracellular signaling cascade in rat liver regeneration.Scandinavian journal of gastroenterology · 2009Article
- Differential expression of GADD45beta in normal and osteoarthritic cartilage: potential role in homeostasis of articular chondrocytes.Arthritis and rheumatism · 2008Article
- Identification of novel light-induced genes in the suprachiasmatic nucleus.BMC neuroscience · 2007Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study was to investigate if Gadd45b prevents IL-1beta-induced beta cell MAPK signalling and apoptosis. MATERIALS: Rat insulinoma INS-1E cells and mouse beta-TC3 cells stably expressing Gadd45b were generated. The effects of Gadd45b expression on signalling by JNK, ERK and p38 were assessed by Western blotting and kinase assays. Apoptosis rate was measured by terminal deoxynucleotidyl-mediated dUTP-biotin nick end-labelling (TUNEL) and an ELISA designed to detect apoptotic nucleosomes. Expression of endogenous Gadd45b mRNA was measured by RT-PCR.
resultsIn INS-1E and beta-TC3 cells, expression of Gadd45b inhibited IL-1beta-induced activation of JNK and ERK, but augmented IL-1beta-mediated p38 activity. IL-1beta-induced nitric oxide production and decreases in insulin content and secretion were reduced by GADD45beta. IL-1beta-induced apoptosis was reduced by GADD45beta by up to 77%. Although IL-1beta stimulated the time-dependent induction of endogenous Gadd45b in INS-1E cells and rat islets, expression levels were lower in these cells than in IL-1beta-exposed NIH-3T3 and 3DO T cells. CONCLUSIONS/
interpretationInadequate induction of Gadd45b, which encodes a novel beta cell JNK and ERK inhibitor, may in part explain the pro-apoptotic response of beta cells to IL-1beta.
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