Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1 adipocytes

Tetsuya Yamada, Hideki Katagiri, Tomoichiro Asano, Masatoshi Tsuru, Kouichi Inukai, Hiraku Ono, Tatsuhiko Kodama, Masatoshi Kikuchi, Yoshitomo Oka

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

To investigate role of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in the insulin-signaling pathway for glucose metabolism, wild-type (wt), the kinase-dead (kd), or the plecstrin homology (PH) domain deletion (APH) mutant of PDK1 was expressed using an adenovirus gene transduction system in 3T3-L1 adipocytes. wt-PDK1 and kd-PDK1 were found in both membrane and cytosol fractions, whereas APH-PDK1, which exhibited PDK1 activity similar to that of wt-PDK1, was detected exclusively in the cytosol fraction. Insulin dose dependently activated protein kinase B (PKB) but did not change atypical protein kinase C (aPKC) activity in control cells. aPKC activity was not affected by expression of wt-, kd-, or APH-PDK1 in either the presence or the absence of insulin. Overexpression of wt-PDK1 enhanced insulin-induced activation of PKB as well as insulin-induced phosphorylation of glycogen synthase kinase (GSK)3α/β, a direct downstream target of PKB, although insulin-induced glycogen synthesis was not significantly enhanced by wt-PDK1 expression. Neither APH-PDK1 nor kd-PDK1 expression affected PKB activity, GSK3 phosphorylation, or glycogen synthesis. Thus membrane localization of PDK1 via its PH domain is essential for insulin signaling through the PDK1-PKB-GSK3α/β pathway. Glucose transport activity was unaffected by expression of wt-PDK1, kd-PDK1, or APH-PDK1 in either the presence or the absence of insulin. These findings suggest the presence of a signaling pathway for insulin-stimulated glucose transport in which PDK1 to PKB or aPKC is not involved.

Original languageEnglish
Pages (from-to)E1385-E1394
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number6 45-6
DOIs
Publication statusPublished - 2002

Keywords

  • GLUT4
  • Glucose transport
  • Glycogen synthesis
  • Protein kinase B
  • Protein kinase C

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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