Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells

Hye Jeong Lee, Jung Ok Lee, Yong Woo Lee, Shin Ae Kim, Sun-Hwa Park, Hyeon Soo Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Follistatin-like 1 (FSTL-1) is a novel myokine; however, little is known about its metabolic role. Here, FSTL-1 stimulated glucose uptake in an AMP-activated protein kinase (AMPK)-dependent manner in L6 rat skeletal muscle cells. FSTL-1 increased intracellular calcium concentration. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) inhibition blocked FSTL-1-induced AMPK phosphorylation and glucose uptake. In addition, FSTL-1 stimulated the phosphorylation of p21-activated kinase 1 (PAK1), a small GTPase Rac1 downstream protein. PAK1 knockdown or inhibition of Rac1 blocked FSTL-1-induced glucose uptake; moreover, kalirin, a Rac1 guanine nucleotide exchange factor (GEF), was induced by FSTL-1. Kalirin knockdown with siRNA blocked FSTL-1-induced PAK1 phosphorylation and glucose uptake. Consistent with the induction of Rac1 GEF kalirin, the GTP-bound form of Rac1 was increased by FSTL-1. FSTL-1 increased the production of glucose transporter type 4 (GLUT4) protein and also stimulated the translocation of GLUT4 to the plasma membrane. Translocation of GLUT4 was not observed in cells pre-treated with AMPK inhibitor, Rac1 inhibitor, or kalirin siRNA. In primary myoblast cell culture, FSTL-1 increased glucose uptake in an AMPK-dependent manner. A CaMKK inhibitor or kalirin knockdown blocked FSTL-1-induced glucose uptake. These results suggest that kalirin and Rac1 GEF play important roles in FSTL-1-mediated glucose regulation in skeletal muscle cells.

Original languageEnglish
Pages (from-to)150-157
Number of pages8
JournalCellular Signalling
Volume29
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • AMPK
  • GEF
  • Glucose
  • Kalirin
  • Myokine
  • Small GTPase

ASJC Scopus subject areas

  • Cell Biology

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