ArticleDiabetologia2016
Autophagy is a major regulator of beta cell insulin homeostasis.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 144 citations in OpenAlex.
- Trial
- Mitochondria-Endoplasmic Reticulum Crosstalk in Pancreatic β-Cell Stress: A Driver of Diabetes.Cells · 2026Review
- Stathmin-2 mediates paracrine hormone regulation of glucagon through lysosomal trafficking in αTC1-6 cells.The Journal of physiology · 2026Article
- Crinophagy in Pancreatic Beta Cells: From Insulin Granule Turnover to Diabetes Pathogenesis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Oleanolic Acid Ameliorates Hepatic Lipid Metabolism and Autophagy in Type 2 Diabetic Mice via the STAT3 Signaling Pathway.Food science & nutrition · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- Diabetes, Protein Misfolding, and Heat Stress: Molecular Insights and Translational Perspectives.TH open : companion journal to thrombosis and haemostasis · 2026Review
- Article
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- The role of angiotensin (1-7) in pancreatic β-cell function and survival: A focus on autophagy.Medicine · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity.Frontiers in immunology · 2025Article
- Pathology and Treatments of Alzheimer's Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes.Molecules (Basel, Switzerland) · 2024Review
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Review
- Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.eGastroenterology · 2024Article
- Autophagy alterations in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease: the evidence from human studies.Internal and emergency medicine · 2024Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
aims/hypothesisWe studied the role of protein degradation pathways in the regulation of insulin production and secretion and hypothesised that autophagy regulates proinsulin degradation, thereby modulating beta cell function.
methodsProinsulin localisation in autophagosomes was demonstrated by confocal and electron microscopy. Autophagy was inhibited by knockdown of autophagy-related (ATG) proteins and using the H(+)-ATPase inhibitor bafilomycin-A1. Proinsulin and insulin content and secretion were assessed in static incubations by ELISA and RIA.
resultsConfocal and electron microscopy showed proinsulin localised in autophagosomes and lysosomes. Beta-Atg7 (-/-) mice had proinsulin-containing sequestosome 1 (p62 [also known as SQSTM1])(+) aggregates in beta cells, indicating proinsulin is regulated by autophagy in vivo. Short-term bafilomycin-A1 treatment and ATG5/7 knockdown increased steady-state proinsulin and hormone precursor chromogranin A content. ATG5/7 knockdown also increased glucose- and non-fuel-stimulated insulin secretion. Finally, mutated forms of proinsulin that are irreparably misfolded and trapped in the endoplasmic reticulum are more resistant to degradation by autophagy. CONCLUSIONS/
interpretationIn the beta cell, transport-competent secretory peptide precursors, including proinsulin, are regulated by autophagy, whereas efficient clearance of transport-incompetent mutated forms of proinsulin by alternative degradative pathways may be necessary to avoid beta cell proteotoxicity. Reduction of autophagic degradation of proinsulin increases its residency in the secretory pathway, followed by enhanced secretion in response to stimuli.
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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.