title: Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells.
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.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: anatomykim@korea.ac.kr.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D038702:Follistatin-Related Proteins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D038702:Follistatin-Related Proteins; D051275:Glucose Transporter Type 4; D020662:Guanine Nucleotide Exchange Factors; C102365:Kalrn protein, rat; D054462:p21-Activated Kinases; D055372:AMP-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D005947:Glucose; D002118:Calcium
keywords: AMPK; GEF; Glucose; Kalirin; Myokine; Small GTPase