1773-P: Beta-Catenin Is a Key Player in Insulin-Stimulated Skeletal Muscle Glucose Transport

Abstract

Recent work has identified β-catenin as a potential regulator of vesicle trafficking within various tissues including synapses, pancreatic β-cells, and adipocytes. The trafficking of GLUT4 vesicles to the cell membrane is essential for insulin-stimulated glucose uptake. Here we provide evidence for a role of β-catenin in regulating skeletal muscle glucose transport. In in vivo models, β-catenin is sensitive to insulin, which through PI3 kinase and Akt triggers phosphorylation of β-catenin at serine 552 (S552). Substituting S552 to alanine impairs glucose transport in L6-GLUT4-myc cells suggesting S552 is key in β-catenin-regulated glucose transport. Furthermore, inhibition of β-catenin in ex vivo models and cell culture impairs insulin-stimulated glucose transport. Using transcriptional inhibitors we demonstrate that β-catenin’s regulation of glucose transport is at least in part independent of its role in gene regulation. Finally, we investigated whether diet induced insulin-resistance alters insulin stimulated β-cateninS552 phosphorylation in vivo. Based on β-catenin’s structure and role in other cellular processes we believe that β-catenin regulates glucose transport via interactions with cytoskeletal proteins which ultimately regulate vesicle movement. Disclosure S.W.C. Masson: None. P.R. Shepherd: None. T.L. Merry: None. Funding Royal Society of New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery