ArticleCell metabolism2006
GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress.
Article in Cell metabolism, 2006. 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 222 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
222 citing papers in PubMed, 1 synthesis or guideline pooled it, 432 citations in OpenAlex.
- A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists.Frontiers in endocrinology · 2025Pooled it
- Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study.The Journal of clinical endocrinology and metabolism · 2021Trial
- Proteostasis in the regulation of pancreatic islet cell plasticity.Journal of diabetes investigation · 2026Review
- Article
- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- The molecular mechanisms of incretin resistance in Type 2 Diabetes Mellitus (T2DM).Nutrition & diabetes · 2026Review
- Transient ER stress cell-autonomously promotes beta cell cycling in mice.Diabetologia · 2026Article
- Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm.Diabetes, obesity & metabolism · 2026Review
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- β-Cell Mitochondrial Dysfunction: Underlying Mechanisms and Potential Therapeutic Strategies.Cells · 2025Review
- Targeting Metabolic Dysfunction in Parkinson's Disease: The Role of GLP-1 Agonists in Body Weight Regulation and Neuroprotection.Current diabetes reports · 2025Review
- Metabolic Reprogramming Through Polyphenol Networks: A Systems Approach to Metabolic Inflammation and Insulin Resistance.Medical sciences (Basel, Switzerland) · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Article
- Characterization of Novel WFS1 Variants in Three Diabetes Pedigrees.Journal of diabetes · 2025Article
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- GLP-1-based therapies for type 2 diabetes: from single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation.Diabetology & metabolic syndrome · 2025Review
- Targeting Ferroptosis in Parkinson's: Repurposing Diabetes Drugs as a Promising Treatment.International journal of molecular sciences · 2025Review
- A novel heterozygous WFS1 variant of uncertain significance in a patient with early-onset diabetes: a case report.Frontiers in endocrinology · 2025Article
- A new link between insulinoma and congenital glucose-galactose malabsorption.Endocrine oncology (Bristol, England) · 2025Article
162 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin biosynthesis, beta cell survival, and glucose homeostasis. We show that a murine model of diabetes is associated with the development of ER stress in beta cells and that treatment with the GLP-1R agonist exendin-4 significantly reduced biochemical markers of islet ER stress in vivo. Exendin-4 attenuated translational downregulation of insulin and improved cell survival in purified rat beta cells and in INS-1 cells following induction of ER stress in vitro. GLP-1R agonists significantly potentiated the induction of ATF-4 by ER stress and accelerated recovery from ER stress-mediated translational repression in INS-1 beta cells in a PKA-dependent manner. The effects of exendin-4 on the induction of ATF-4 were mediated via enhancement of ER stress-stimulated ATF-4 translation. Moreover, exendin-4 reduced ER stress-associated beta cell death in a PKA-dependent manner. These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival.
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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.