ArticleAutophagy2022
Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
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- Association of GLP1RAs with risk of chronic obstructive pulmonary disease: evidence from drug target Mendelian randomization.Diabetology & metabolic syndrome · 2025Article
- SMURF1 mediates damaged lysosomal homeostasis by ubiquitinating PPP3CB to promote the activation of TFEB.Autophagy · 2025Article
- Dysregulated autophagy at the nexus of type 2 diabetes mellitus and pancreatic cancer pathogenesis.Frontiers in endocrinology · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- (-)-Epigallocatechin 3-gallate protects pancreatic β-cell against excessive autophagy-induced injury through promoting FTO degradation.Autophagy · 2024Article
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner.Diabetes & metabolism journal · 2024Article
- Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal CaExperimental & molecular medicine · 2023Review
- Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer's Disease and Parkinson's Disease.Aging and disease · 2023Review
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- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- Secretory autophagy promotes RAB37-mediated insulin secretion under glucose stimulation bothAutophagy · 2023Article
- Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.Frontiers in endocrinology · 2023Article
- GLP-1 receptor agonists as promising disease-modifying agents in WFS1 spectrum disorder.Frontiers in clinical diabetes and healthcare · 2023Review
- Role of Autophagy in the Pathogenesis of Diabetes and Therapeutic Potential of Autophagy Modulators in the Treatment of Diabetes and Metabolic Syndrome.Journal of Korean medical science · 2022Review
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Macroautophagy/autophagy is critical for the regulation of pancreatic β-cell mass and its deregulation has been implicated in the pathogenesis of type 2 diabetes (T2D). We have previously shown that treatment of pancreatic β-cells with the GLP1R (glucagon like peptide 1 receptor) agonist exendin-4 stimulates autophagic flux in a setting of chronic nutrient excess. The aim of this study was to identify the underlying pathways contributing to enhanced autophagic flux.Pancreatic β-cells (INS-1E),mouse and human islets were treated with glucolipotoxic stress (0.5 mM palmitate and 25 mM glucose) in the presence of exendin-4. Consistent with our previous work, exendin-4 stimulated autophagic flux. Using chemical inhibitors and siRNA knockdown, we identified RAPGEF4/EPAC2 (Rap guanine nucleotide exchange factor 4) and downstream calcium signaling to be essential for regulation of autophagic flux by exendin-4. This pathway was independent of AMPK and MTOR signaling. Further analysis identified PPP3/calcineurin and its downstream regulator TFEB (transcription factor EB) as key proteins mediating exendin-4 induced autophagy. Importantly, inhibition of this pathway prevented exendin-4-mediated cell survival and overexpression of TFEB mimicked the cell protective effects of exendin-4 in INS-1E and human islets. Moreover, treatment of
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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 Socratic graph.