The Rab GTPase-activating protein AS160 as a common regulator of insulin- and Gαq-mediated intracellular GLUT4 vesicle distribution

Tomoyuki Yuasa, Keiji Uchiyama, Yuko Ogura, Masafumi Kimura, Kiyoshi Teshigawara, Toshio Hosaka, Yoshinori Tanaka, Toshiyuki Obata, Hiroyuki Sano, Kazushiro Kishi, Yousuke Ebina

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11 Citations (Scopus)

Abstract

Akt substrate of 160kDa (AS160) is a Rab GTPase activating protein (GAP) and was recently identified as a component of the insulin signaling pathway of glucose transporter type 4 (GLUT4) translocation. we and others, previously reported that the activation of Gαq protein-coupled receptors (GαqPCRs) also stimulated GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GαqPCRs also promoted phosphorylation of AS160 by the 5′-AMP activated protein kinase (AMPK). The suppression of AS160 phosphorylation by the siRNA mediated AMPKα1 subunit knockdown promoted GLUT4 vesicle retention in intracellular compartments. This suppression did not affect the ratio of non-induced cell surface GLUT4 to Gαq-induced it. Rat 3Y1 cells lacking AS160 did not show insulin-induced GLUT4 translocation. The cells stably expressing GLUT4 revealed GLUT4 vesicles that were mainly localized in the perinuclear region and less frequently on the cell surface. After expression of exogenous AS160, GLUT4 on the cell surface decreased and GLUT4 vesicles were redistributed throughout the cytoplasm. Although PMA-induced or sodium fluoride-induced GLUT4 translocation was significantly increased in these cells, insulin did not affect GLUT4 translocation. These results suggest that AS160 is a common regulator of insulin- and GαqPCR activation-mediated GLUT4 distribution in the cells.

Original languageEnglish
Pages (from-to)345-359
Number of pages15
JournalEndocrine Journal
Volume56
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Keywords

  • AMPK
  • AS160
  • Gαq protein-coupled receptor
  • GLUT4

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Yuasa, T., Uchiyama, K., Ogura, Y., Kimura, M., Teshigawara, K., Hosaka, T., Tanaka, Y., Obata, T., Sano, H., Kishi, K., & Ebina, Y. (2009). The Rab GTPase-activating protein AS160 as a common regulator of insulin- and Gαq-mediated intracellular GLUT4 vesicle distribution. Endocrine Journal, 56(3), 345-359. https://doi.org/10.1507/endocrj.K08E-216