ArticleThe Journal of biological chemistry2010
Inhibition of deoxyhypusine synthase enhances islet {beta} cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05594563 (TArgeting Type 1 Diabetes Using POLyamines), which is not on this map. Cited by 30 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.
TArgeting Type 1 Diabetes Using POLyamines (TADPOL): A Randomized, Double-Masked, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Difluoromethylornithine (DFMO) to Preserve Insulin Production in Type 1 Diabetes
Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- A role for eIF5A in translational control of stress-inducible proteins in multiple myeloma cell lines.Molecular oncology · 2026Article
- Blood DNA methylation of EIF5A and TGIF1 is associated with adipose tissue health and metabolic outcomes in obesity: a multi-cohort study.Clinical epigenetics · 2026Article
- Mitochondria serve as a holdout compartment for aggregation-prone proteins hindering efficient degradation.Nature communications · 2026Article
- Article
- Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.Metabolites · 2022Review
- The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.Cell & bioscience · 2021Review
- Deoxyhypusine synthase promotes a pro-inflammatory macrophage phenotype.Cell metabolism · 2021Article
- Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.Nature communications · 2021Article
- Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus.Bioscience reports · 2021Article
- Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney.Cell death & disease · 2021Article
- Hypusinated eIF5A is expressed in the pancreas and spleen of individuals with type 1 and type 2 diabetes.PloS one · 2020Article
- Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.Science signaling · 2019Article
- Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology.International journal of molecular sciences · 2018Review
- Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial Silencing and Improves Kidney Transplant Outcome.Journal of the American Society of Nephrology : JASN · 2017Article
- Peroxisome Proliferator-activated Receptor-γ Activation Augments the β-Cell Unfolded Protein Response and Rescues Early Glycemic Deterioration and β Cell Death in Non-obese Diabetic Mice.The Journal of biological chemistry · 2016Article
- Targeting the polyamine-hypusine circuit for the prevention and treatment of cancer.Amino acids · 2016Review
- Global quantitative proteomics reveal up-regulation of endoplasmic reticulum stress response proteins upon depletion of eIF5A in HeLa cells.Scientific reports · 2016Article
- Transcriptional activity of the islet β cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9.The Journal of biological chemistry · 2015Article
- Maintenance of Pdx1 mRNA translation in islet β-cells during the unfolded protein response.Molecular endocrinology (Baltimore, Md.) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Islet β cell dysfunction resulting from inflammation, ER stress, and oxidative stress is a key determinant in the progression from insulin resistance to type 2 diabetes mellitus. It was recently shown that the enzyme deoxyhypusine synthase (DHS) promotes early cytokine-induced inflammation in the β cell. DHS catalyzes the conversion of lysine to hypusine, an amino acid that is unique to the translational elongation factor eIF5A. Here, we sought to determine whether DHS activity contributes to β cell dysfunction in models of type 2 diabetes in mice and β cell lines. A 2-week treatment of obese diabetic C57BLKS/J-db/db mice with the DHS inhibitor GC7 resulted in improved glucose tolerance, increased insulin release, and enhanced β cell mass. Thapsigargin treatment of β cells in vitro induces a picture of ER stress and apoptosis similar to that seen in db/db mice; in this setting, DHS inhibition led to a block in CHOP (CAAT/enhancer binding protein homologous protein) production despite >30-fold activation of Chop gene transcription. Blockage of CHOP translation resulted in reduction of downstream caspase-3 cleavage and near-complete protection of cells from apoptotic death. DHS inhibition appeared to prevent the cytoplasmic co-localization of eIF5A with the ER, possibly precluding the participation of eIF5A in translational elongation at ER-based ribosomes. We conclude that hypusination by DHS is required for the ongoing production of proteins, particularly CHOP, in response to ER stress in the β cell.
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.