ArticleDiabetes2013
Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
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- Crosstalk between autophagy and ferroptosis in diabetes.Genes & diseases · 2026Review
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
- Regulation of m6A methylation in the immune microenvironment in the development of diabetes mellitus.Journal of translational medicine · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.eGastroenterology · 2024Article
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 2024Review
- DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells.Journal of translational medicine · 2024Article
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- Complement: Functions, location and implications.Immunology · 2023Review
- Review
- Qizhi Jiangtang capsule activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes.Developmental cell · 2023Article
- Amyloid β-Peptide Effects on Glucose Regulation Are Dependent on Apolipoprotein E Genotype.eNeuro · 2023Article
- Synchronized proinsulin trafficking reveals delayed Golgi export accompanies β-cell secretory dysfunction in rodent models of hyperglycemia.Scientific reports · 2023Article
50 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of misfolded proinsulin in the β-cell leads to dysfunction induced by endoplasmic reticulum (ER) stress, with diabetes as a consequence. Autophagy helps cellular adaptation to stress via clearance of misfolded proteins and damaged organelles. We studied the effects of proinsulin misfolding on autophagy and the impact of stimulating autophagy on diabetes progression in Akita mice, which carry a mutation in proinsulin, leading to its severe misfolding. Treatment of female diabetic Akita mice with rapamycin improved diabetes, increased pancreatic insulin content, and prevented β-cell apoptosis. In vitro, autophagic flux was increased in Akita β-cells. Treatment with rapamycin further stimulated autophagy, evidenced by increased autophagosome formation and enhancement of autophagosome-lysosome fusion. This was associated with attenuation of cellular stress and apoptosis. The mammalian target of rapamycin (mTOR) kinase inhibitor Torin1 mimicked the rapamycin effects on autophagy and stress, indicating that the beneficial effects of rapamycin are indeed mediated via inhibition of mTOR. Finally, inhibition of autophagy exacerbated stress and abolished the anti-ER stress effects of rapamycin. In conclusion, rapamycin reduces ER stress induced by accumulation of misfolded proinsulin, thereby improving diabetes and preventing β-cell apoptosis. The beneficial effects of rapamycin in this context strictly depend on autophagy; therefore, stimulating autophagy may become a therapeutic approach for 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.