ArticleDiabetes2015
Antioxidants Complement the Requirement for Protein Chaperone Function to Maintain β-Cell Function and Glucose Homeostasis.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 51 citations in OpenAlex.
- Coordinated expression and assembly of BiP, p58Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by BiallelicInternational journal of molecular sciences · 2024Article
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- Neuronal p58Cells · 2023Article
- Modulation of Unfolded Protein Response Restores Survival and Function of β-Cells Exposed to the Endocrine Disruptor Bisphenol A.International journal of molecular sciences · 2023Article
- Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.Biomolecules · 2022Review
- ER Redox Homeostasis Regulates Proinsulin Trafficking and Insulin Granule Formation in the Pancreatic Islet β-Cell.Function (Oxford, England) · 2022Article
- Dual topology of co-chaperones at the membrane of the endoplasmic reticulum.Cell death discovery · 2021Review
- Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Surfactant protein C mutation links postnatal type 2 cell dysfunction to adult disease.JCI insight · 2021Article
- Case Report: HomozygousFrontiers in endocrinology · 2021Article
- Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.Progress in molecular and subcellular biology · 2021Article
- Mitochondrial dysfunction and pancreatic islet β-cell failure (Review).Experimental and therapeutic medicine · 2020Review
- Characterization of the 5'-flanking region of the human and mouse CHAC1 genes.Biochemistry and biophysics reports · 2020Article
- Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding.Diabetes · 2020Article
- The Impact of the ER Unfolded Protein Response on Cancer Initiation and Progression: Therapeutic Implications.Advances in experimental medicine and biology · 2020Review
- Contribution of Oxidative Stress and Impaired Biogenesis of Pancreatic β-Cells to Type 2 Diabetes.Antioxidants & redox signaling · 2019Article
- Article
- Biosynthesis, structure, and folding of the insulin precursor protein.Diabetes, obesity & metabolism · 2018Review
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
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 2 countries.
Funding
Abstract
Proinsulin misfolding in the endoplasmic reticulum (ER) initiates a cell death response, although the mechanism(s) remains unknown. To provide insight into how protein misfolding may cause β-cell failure, we analyzed mice with the deletion of P58(IPK)/DnajC3, an ER luminal co-chaperone. P58(IPK-/-) mice become diabetic as a result of decreased β-cell function and mass accompanied by induction of oxidative stress and cell death. Treatment with a chemical chaperone, as well as deletion of Chop, improved β-cell function and ameliorated the diabetic phenotype in P58(IPK-/-) mice, suggesting P58(IPK) deletion causes β-cell death through ER stress. Significantly, a diet of chow supplemented with antioxidant dramatically and rapidly restored β-cell function in P58(IPK-/-) mice and corrected abnormal localization of MafA, a critical transcription factor for β-cell function. Antioxidant feeding also preserved β-cell function in Akita mice that express mutant misfolded proinsulin. Therefore defective protein folding in the β-cell causes oxidative stress as an essential proximal signal required for apoptosis in response to ER stress. Remarkably, these findings demonstrate that antioxidant feeding restores cell function upon deletion of an ER molecular chaperone. Therefore antioxidant or chemical chaperone treatment may be a promising therapeutic approach for type 2 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.