ArticleDiabetes2009
Glucagon-like peptide-1 agonists protect pancreatic beta-cells from lipotoxic endoplasmic reticulum stress through upregulation of BiP and JunB.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02882477 (Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy), which is not on this map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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.
Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy
Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review.The Libyan journal of medicine · 2013Pooled it
- The β-cells in type 1 diabetes mellitus: findings from human pancreas studies.Nature reviews. Endocrinology · 2026Review
- GLP-1 Receptor Agonists as Molecular Relievers of Lipotoxic Stress: From Pancreatic Beta-Cell Cholesterol Efflux to Systemic and Tissue-Specific Metabolic Protection.International journal of molecular sciences · 2026Review
- JNK and p53 cause human and mouse β cell death during excessive unfolded protein response.The Journal of clinical investigation · 2026Article
- Engineering single-dose plasmid DNA for sustained in vivo delivery of designer incretins.Trends in biotechnology · 2026Article
- Transient ER stress cell-autonomously promotes beta cell cycling in mice.Diabetologia · 2026Article
- Valvular Leaflets Are Not Innocent Bystanders: Divergent Fibrotic Remodeling Accompanies Functional Mitral and Tricuspid Regurgitation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- GLP-1 receptor and Mitochondria-ER Contact Sites: an emerging mechanism of metabolic regulation.Frontiers in physiology · 2026Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Pharmacological and non-pharmacological modulation of endoplasmic reticulum stress in pediatric diabetes.Frontiers in endocrinology · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Synergistic therapeutic strategies for metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus: molecular insights and clinical advances.Frontiers in endocrinology · 2025Review
- Mechanistic Pathways and Clinical Implications of GLP-1 Receptor Agonists in Type 1 Diabetes Management.International journal of molecular sciences · 2024Review
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- The Regulation of Metabolic Homeostasis by Incretins and the Metabolic Hormones Produced by Pancreatic Islets.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models.Diabetologia · 2023Article
- Review
- GLP-1 receptor agonists as promising disease-modifying agents in WFS1 spectrum disorder.Frontiers in clinical diabetes and healthcare · 2023Review
52 more citing papers are in PubMed but not listed here.
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 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveChronic exposure of pancreatic beta-cells to saturated free fatty acids (FFAs) causes endoplasmic reticulum (ER) stress and apoptosis and may contribute to beta-cell loss in type 2 diabetes. Here, we evaluated the molecular mechanisms involved in the protection of beta-cells from lipotoxic ER stress by glucagon-like peptide (GLP)-1 agonists utilized in the treatment of type 2 diabetes. RESEARCH DESIGN AND
methodsINS-1E or fluorescence-activated cell sorter-purified primary rat beta-cells were exposed to oleate or palmitate with or without the GLP-1 agonist exendin-4 or forskolin. Cyclopiazonic acid was used as a synthetic ER stressor, while the activating transcription factor 4-C/EBP homologous protein branch was selectively activated with salubrinal. The ER stress signaling pathways modulated by GLP-1 agonists were studied by real-time PCR and Western blot. Knockdown by RNA interference was used to identify mediators of the antiapoptotic GLP-1 effects in the ER stress response and downstream mitochondrial cell death mechanisms.
resultsExendin-4 and forskolin protected beta-cells against FFAs via the induction of the ER chaperone BiP and the antiapoptotic protein JunB that mediate beta-cell survival under lipotoxic conditions. On the other hand, exendin-4 and forskolin protected against synthetic ER stressors by inactivating caspase 12 and upregulating Bcl-2 and X-chromosome-linked inhibitor of apoptosis protein that inhibit mitochondrial apoptosis.
conclusionsThese observations suggest that GLP-1 agonists increase in a context-dependent way the beta-cell defense mechanisms against different pathways involved in ER stress-induced apoptosis. The identification of the pathways modulated by GLP-1 agonists allows for targeted approaches to alleviate beta-cell ER stress in 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.