ArticleThe Journal of biological chemistry2015
Inhibition of autophagic turnover in β-cells by fatty acids and glucose leads to apoptotic cell death.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 126 citations in OpenAlex.
- Targeting endoplasmic reticulum export disrupts metabolic resilience in multiple myeloma.Signal transduction and targeted therapy · 2026Article
- Caveolin-1 deficiency improved glucose metabolism via modulation of β-cell autophagy in high-fat diet-fed mice.The Journal of biological chemistry · 2026Article
- Neuregulin 4 in Insulin Resistance: Mechanisms, Controversies, and Therapeutic Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Lysosomal dysfunction in diabetes and diabetic complications.Frontiers in endocrinology · 2026Review
- Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved.Reviews in endocrine & metabolic disorders · 2025Review
- Rescuing lysosomal/autophagic defects via nanoapproach: implications for lysosomal/autophagic defect-related diseases.Journal of Zhejiang University. Science. B · 2025Review
- FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.Science advances · 2025Article
- Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f cells.FEBS open bio · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- Pancreatic β-cell Dysfunction and Diabetes.Juntendo medical journal · 2025Review
- Neuregulin 4 attenuates pancreatic β-cell apoptosis induced by lipotoxicity via activating mTOR-mediated autophagy.Islets · 2024Article
- Role of Autophagy in Type 2 Diabetes Mellitus: The Metabolic Clash.Journal of cellular and molecular medicine · 2024Review
- Protector Role of Cx30.2 in Pancreatic β-Cell against Glucotoxicity-Induced Apoptosis.Biology · 2024Article
- Article
- 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
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Mechanism of Obesity-Related Lipotoxicity and Clinical Perspective.Advances in experimental medicine and biology · 2024Review
- Luteolin Protects Pancreatic β Cells against Apoptosis through Regulation of Autophagy and ROS Clearance.Pharmaceuticals (Basel, Switzerland) · 2023Article
- From Diabetes to Diabetic Complications: Role of Autophagy.Current medical science · 2023Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Autophagy, a cellular recycling process responsible for turnover of cytoplasmic contents, is critical for maintenance of health. Defects in this process have been linked to diabetes. Diabetes-associated glucotoxicity/lipotoxicity contribute to impaired β-cell function and have been implicated as contributing factors to this disease. We tested the hypothesis that these two conditions affect β-cell function by modulating autophagy. We report that exposure of β-cell lines and human pancreatic islets to high levels of glucose and lipids blocks autophagic flux and leads to apoptotic cell death. EM analysis showed accumulation of autophagy intermediates (autophagosomes), with abundant engulfed cargo in palmitic acid (PA)- or glucose-treated cells, indicating suppressed autophagic turnover. EM studies also showed accumulation of damaged mitochondria, endoplasmic reticulum distention, and vacuolar changes in PA-treated cells. Pulse-chase experiments indicated decreased protein turnover in β-cells treated with PA/glucose. Expression of mTORC1, an inhibitor of autophagy, was elevated in β-cells treated with PA/glucose. mTORC1 inhibition, by treatment with rapamycin, reversed changes in autophagic flux, and cell death induced by glucose/PA. Our results indicate that nutrient toxicity-induced cell death occurs via impaired autophagy and is mediated by activation of mTORC1 in β-cells, contributing to β-cell failure in the presence of metabolic stress.
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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.