ArticleThe Journal of cell biology2024
Integrated stress response activator halofuginone protects mice from diabetes-like phenotypes.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed.
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Tuning tRNA synthetase inhibition reveals parabolic induction of stress granules limited in size and RNA content.RNA (New York, N.Y.) · 2026Article
- Article
- Roles of the integrated stress response in regulation of inflammatory reactions.Frontiers in immunology · 2026Review
- Review
- Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Traditional medicine meets modern science: Halofuginone's role in combating autoimmune diseases.Journal of natural medicines · 2025Review
- Drug Repurposing Screen Identifies an HRI Activating Compound that Promotes Adaptive Mitochondrial Remodeling in MFN2-deficient Cells.bioRxiv : the preprint server for biology · 2025Article
- The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21.Science advances · 2025Article
- TUDCA modulates drug bioavailability to regulate resistance to acute ER stress inMolecular biology of the cell · 2025Article
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.
Funding
Abstract
The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience and protect cells from challenges. Here, we investigated whether increasing ISR signaling could rescue diabetes-like phenotypes in a mouse model of diet-induced obesity (DIO). We show that the orally available and clinically approved GCN2 activator halofuginone (HF) can activate the ISR in mouse tissues. We found that daily oral administration of HF increases glucose tolerance whilst reducing weight gain, insulin resistance, and serum insulin in DIO mice. Conversely, the ISR inhibitor GSK2656157, used at low doses to optimize its selectivity, aggravates glucose intolerance in DIO mice. Whilst loss of function mutations in mice and humans have revealed that PERK is the essential ISR kinase that protects from diabetes, our work demonstrates the therapeutic value of increasing ISR signaling by activating the related kinase GCN2 to reduce diabetes phenotypes in a DIO mouse model.
Indexed as
Identifiers
What Socratic 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 Socratic graph.