ArticleThe Journal of biological chemistry2014
Prolonged insulin stimulation down-regulates GLUT4 through oxidative stress-mediated retromer inhibition by a protein kinase CK2-dependent mechanism in 3T3-L1 adipocytes.
Article in The Journal of biological chemistry, 2014. 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 47 papers.
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47 citing papers in PubMed, 90 citations in OpenAlex.
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- Dietary bioactive compounds targeting insulin resistance: mechanisms and preventive potential.Frontiers in nutrition · 2026Review
- The mechanistic interplay of reactive oxygen species in metabolic pathways and insulin signaling in type 2 diabetes.Molecular biology reports · 2025Review
- Therapeutic potential of traditional Chinese medicine and mechanisms for the treatment of type 2 diabetes mellitus.Chinese medicine · 2025Review
- Role of oxidative stress in prediabetes development.Biochemistry and biophysics reports · 2025Review
- Leucine-Rich Repeat Kinase 1 Signaling Targets Proteins Critical for Endosome/Lysosome Sorting and Trafficking in Osteoclasts.Biology · 2025Article
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- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Comparison of different insulin resistance surrogates in predicting hyperuricemia in non-diabetic Yi residents in Yunnan Province.Frontiers in endocrinology · 2025Article
- In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.Cardiovascular diabetology · 2024Article
- The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach.Current issues in molecular biology · 2023Review
- Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients' susceptibility to COVID-19 to the possible caution of future global diabetes tsunami.Inflammopharmacology · 2023Review
- Mechanisms of Oxidative Stress in Metabolic Syndrome.International journal of molecular sciences · 2023Review
- A flavonoid-rich fraction ofFrontiers in pharmacology · 2023Article
- Receptor Recycling by Retromer.Molecular and cellular biology · 2023Review
- Diversity of retromer-mediated vesicular trafficking pathways in plants.Frontiers in plant science · 2023Review
- Role of flavonoids in controlling obesity: molecular targets and mechanisms.Frontiers in nutrition · 2023Review
- Potential Roles of mtDNA Mutations in PCOS-IR: A Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Review
- Black pepper oil (Piper nigrum L.) mitigates dexamethasone induced pancreatic damage via modulation of oxidative and nitrosative stress.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although insulin acutely stimulates glucose uptake by promotion of GLUT4 translocation from intracellular compartments to the plasma membrane in adipocytes and muscles, long term insulin stimulation causes GLUT4 depletion that is particularly prominent in the insulin-responsive GLUT4 storage compartment. This effect is caused mainly by accelerated lysosomal degradation of GLUT4, although the mechanism is not fully defined. Here we show that insulin acutely induced dissociation of retromer components from the low density microsomal membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on the activity of protein kinase CK2 but not phosphatidylinositol 3-kinase or extracellular signal-regulated kinase 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif (Vps35-S7A) was resistant to insulin-induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Furthermore, insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner.
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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.