ArticleThe Journal of biological chemistry2014
Insulin-regulated Glut4 translocation: membrane protein trafficking with six distinctive steps.
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. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- Approaching therapy of Alzheimer's disease via the antidiabetic drug liraglutide-a study with streptozotocin intracerebroventricularly treated Wistar rats.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Does GLUT4 Queue? A Mechanistic Mathematical Model for Insulin Response in Adipocytes.Bulletin of mathematical biology · 2025Article
- Study of the Effects of Deuterium-Depleted Water on the Expression of GLUT4 and Insulin Resistance in the Muscle Cell Line C2C12.Biomedicines · 2024Article
- The Distance Between: An Algorithmic Approach to Comparing Stochastic Models to Time-Series Data.Bulletin of mathematical biology · 2024Article
- Flow cytometry protocol for GLUT4-myc detection on cell surfaces.Bioscience reports · 2024Article
- Mechanosensing in Metabolism.Comprehensive Physiology · 2023Review
- Article
- Beyond the Scale: Investigating Adiponectin, ICAM-1, and VCAM-1 as Metabolic Markers in Obese Adolescents with Metabolic Syndrome.Journal of obesity · 2023Article
- Review
- GLUT4 translocation and dispersal operate in multiple cell types and are negatively correlated with cell size in adipocytes.Scientific reports · 2022Article
- Development of Fermented Shrimp Shell Product with Hypoglycemic and Hypolipidemic Effects on Diabetic Rats.Metabolites · 2022Article
- Illumination of the Endogenous Insulin-Regulated TBC1D4 Interactome in Human Skeletal Muscle.Diabetes · 2022Article
- D609 inhibition of phosphatidylcholine-specific phospholipase C attenuates prolonged insulin stimulation-mediated GLUT4 downregulation in 3T3-L1 adipocytes.Journal of physiology and biochemistry · 2022Article
- Characterization of lipoprotein lipase storage vesicles in 3T3-L1 adipocytes.Journal of cell science · 2022Article
- GLUT4 On the move.The Biochemical journal · 2022Article
- Epithelial mesenchymal transition regulator TWIST1 transcription factor stimulates glucose uptake through upregulation of GLUT1, GLUT3, and GLUT12 in vitro.In vitro cellular & developmental biology. Animal · 2021Article
- The insulin centennial-100 years of milestones in biochemistry.The Journal of biological chemistry · 2021Article
- Mitochondrial Antioxidant SkQ1 Has a Beneficial Effect in Experimental Diabetes as Based on the Analysis of Expression of microRNAs and mRNAs for the Oxidative Metabolism Regulators.Antioxidants (Basel, Switzerland) · 2021Article
- Microtubules in insulin action: what's on the tube?Trends in endocrinology and metabolism: TEM · 2021Review
- Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue.Nature communications · 2021Observational
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The trafficking kinetics of Glut4, the transferrin (Tf) receptor, and LRP1 were quantified in adipocytes and undifferentiated fibroblasts. Six steps were identified that determine steady state cell surface Glut4: (i) endocytosis, (ii) degradation, (iii) sorting, (iv) sequestration, (v) release, and (vi) tethering/docking/fusion. Endocytosis of Glut4 is 3 times slower than the Tf receptor in fibroblasts (ken = 0.2 min(-1) versus 0.6 min(-1)). Differentiation decreases Glut4 ken 40% (ken = 0.12 min(-1)). Differentiation also decreases Glut4 degradation, increasing total and cell surface Glut4 3-fold. In fibroblasts, Glut4 is recycled from endosomes through a slow constitutive pathway (kex = 0.025-0.038 min(-1)), not through the fast Tf receptor pathway (kex = 0.2 min(-1)). The kex measured in adipocytes after insulin stimulation is similar (kex = 0.027 min(-1)). Differentiation decreases the rate constant for sorting into the Glut4 recycling pathway (ksort) 3-fold. In adipocytes, Glut4 is also sorted from endosomes into a second exocytic pathway through Glut4 storage vesicles (GSVs). Surprisingly, transfer from endosomes into GSVs is highly regulated; insulin increases the rate constant for sequestration (kseq) 8-fold. Release from sequestration in GSVs is rate-limiting for Glut4 exocytosis in basal adipocytes. AS160 regulates this step. Tethering/docking/fusion of GSVs to the plasma membrane is regulated through an AS160-independent process. Insulin increases the rate of release and fusion of GSVs (kfuseG) 40-fold. LRP1 cycles with the Tf receptor and Glut4 in fibroblasts but predominantly with Glut4 after differentiation. Surprisingly, AS160 knockdown accelerated LRP1 exocytosis in basal and insulin-stimulated adipocytes. These data indicate that AS160 may regulate trafficking into as well as release from GSVs.
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