ArticleDiabetes2017
Glucagon-Like Peptide 1 Protects Pancreatic β-Cells From Death by Increasing Autophagic Flux and Restoring Lysosomal Function.
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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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
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Effects of different hypoglycaemic drugs on beta-cell function in type 2 diabetes mellitus: a systematic review and network meta-analysis.European journal of medical research · 2025Pooled it
- GLP-1 and Parkinson's Disease: A Comprehensive Review of Biology, Mechanisms and Efficacy.Cells · 2026Review
- Intracellular Calcium Dysregulation: The Hidden Culprit in the Diabetes-Gout Nexus.Biomedicines · 2025Review
- The Roles of Autophagy in Oxidative Stress.Archives of Razi Institute · 2025Review
- Therapeutic potential of traditional Chinese medicine and mechanisms for the treatment of type 2 diabetes mellitus.Chinese medicine · 2025Review
- Association of GLP1RAs with risk of chronic obstructive pulmonary disease: evidence from drug target Mendelian randomization.Diabetology & metabolic syndrome · 2025Article
- Molecular Insights into the Potential Cardiometabolic Effects of GLP-1 Receptor Analogs and DPP-4 Inhibitors.International journal of molecular sciences · 2025Review
- Article
- Disease-modifying pharmacological treatments of type 1 diabetes: Molecular mechanisms, target checkpoints, and possible combinatorial treatments.Pharmacological reviews · 2025Review
- Exendin-4 Reduces Senescence of Inflammation-Induced Periodontal Ligament Stem Cells Through SIRT1/Notch1 Signaling.Stem cells international · 2025Article
- Dysregulated autophagy at the nexus of type 2 diabetes mellitus and pancreatic cancer pathogenesis.Frontiers in endocrinology · 2025Review
- GLP-1 receptor agonists: exploration of transformation from metabolic regulation to multi-organ therapy.Frontiers in pharmacology · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- (-)-Epigallocatechin 3-gallate protects pancreatic β-cell against excessive autophagy-induced injury through promoting FTO degradation.Autophagy · 2024Article
- Programmed cell death and melatonin: A comprehensive review.Functional & integrative genomics · 2024Review
- Puerarin ameliorates high glucose-induced MIN6 cell injury by activating PINK1/Parkin-mediated mitochondrial autophagy.Heliyon · 2024Article
- The role of glucagon-like peptide-1/GLP-1R and autophagy in diabetic cardiovascular disease.Pharmacological reports : PR · 2024Review
- New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.Diagnostics (Basel, Switzerland) · 2024Article
- Acidic Nanoparticles Restore Lysosomal Acidification and Rescue Metabolic Dysfunction in Pancreatic β-Cells under Lipotoxic Conditions.ACS nano · 2024Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Studies in animal models of type 2 diabetes have shown that glucagon-like peptide 1 (GLP-1) receptor agonists prevent β-cell loss. Whether GLP-1 mediates β-cell survival via the key lysosomal-mediated process of autophagy is unknown. In this study, we report that treatment of INS-1E β-cells and primary islets with glucolipotoxicity (0.5 mmol/L palmitate and 25 mmol/L glucose) increases LC3 II, a marker of autophagy. Further analysis indicates a blockage in autophagic flux associated with lysosomal dysfunction. Accumulation of defective lysosomes leads to lysosomal membrane permeabilization and release of cathepsin D, which contributes to cell death. Our data further demonstrated defects in autophagic flux and lysosomal staining in human samples of type 2 diabetes. Cotreatment with the GLP-1 receptor agonist exendin-4 reversed the lysosomal dysfunction, relieving the impairment in autophagic flux and further stimulated autophagy. Small interfering RNA knockdown showed the restoration of autophagic flux is also essential for the protective effects of exendin-4. Collectively, our data highlight lysosomal dysfunction as a critical mediator of β-cell loss and shows that exendin-4 improves cell survival via restoration of lysosomal function and autophagic flux. Modulation of autophagy/lysosomal homeostasis may thus define a novel therapeutic strategy for type 2 diabetes, with the GLP-1 signaling pathway as a potential focus.
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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.