Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells
- Authors
- Lee, Hye Jeong; Lee, Jung Ok; Lee, Yong Woo; Kim, Shin Ae; Park, Sun Hwa; Kim, Hyeon Soo
- Issue Date
- Jan-2017
- Publisher
- Elsevier BV
- Keywords
- AMPK; GEF; Glucose; Kalirin; Myokine; Small GTPase
- Citation
- Cellular Signalling, v.29, pp 150 - 157
- Pages
- 8
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Cellular Signalling
- Volume
- 29
- Start Page
- 150
- End Page
- 157
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/5428
- DOI
- 10.1016/j.cellsig.2016.10.013
- ISSN
- 0898-6568
1873-3913
- 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 Racl 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 Racl GEF kalirin, the GTP-bound form of Racl 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, Racl 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 Racl GEF play important roles in FSTL-1-mediated glucose regulation in skeletal muscle cells. (C) 2016 Elsevier Inc. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 1. Basic Science > Department of Anatomy > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.