p110β Is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity

Tomoichiro Asano, Akira Kanda, Hideki Katagiri, Masao Nawano, Takehide Ogihara, Kouichi Inukai, Motonobu Anai, Yasushi Fukushima, Yoshio Yazaki, Masatoshi Kikuchi, Roya Hooshmand-Rad, Carl Henrik Heldin, Yoshitomo Oka, Makoto Funaki

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Activation of p85/p110 type phosphatidylinositol kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit (e.g. p85α) and one of two widely distributed isoforms of the p110 catalytic subunit: p110α or p110β. In the present study, we compared the two isoforms in the regulation of insulin action. During differentiation of 3T3-L1 cells into adipocytes, p110β was up-regulated ~10-fold, whereas expression of p110α was unaltered. The effects of the increased p110 expression were further assessed by expressing epitope tagged p110β and p110α in 3T3-L1 cells using adenovirus transduction systems, respectively. In vitro, the basal lipid kinase activity of p110β was lower than that of p110α. When p110α and p110β were overexpressed in 3T3-L1 adipocytes, exposing cells to insulin induced each of the subunits to form complexes with p85α and tyrosine- phosphorylated IRS-1 with similar efficiency. However, whereas the kinase activity of p110β, either endogenous or exogeneous, was markedly enhanced by insulin stimulation, only very small increases of the activity of p110α were observed. Interestingly, overexpression of p110β increased insulin-induced glucose uptake by 3T3-L1 cells without significantly affecting basal glucose transport, whereas overexpression of p110α increased both basal and insulin- stimulated glucose uptake. Finally, microinjection of anti-p110β neutralizing antibody into 3T3-L1 adipocytes abolished insulin-induced translocation of GLUT4 to the cell surface almost completely, whereas anti- p110α neutralizing antibody did only slightly. Together, these findings suggest that p110β plays a crucial role in cellular activities evoked acutely by insulin.

Original languageEnglish
Pages (from-to)17671-17676
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number23
DOIs
Publication statusPublished - 2000 Jun 9

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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