title: Visfatin, a novel adipokine, stimulates glucose uptake through the Ca2 +-dependent AMPK-p38 MAPK pathway in C2C12 skeletal muscle cells.
abstract: Visfatin is a novel adipocytokine produced by visceral fat. In the present study, visfatin increased AMP-activated protein kinase (AMPK) phosphorylation in mouse C2C12 skeletal muscle cells. It also increased phosphorylation of the insulin receptor, whose knockdown blocked visfatin-induced AMPK phosphorylation and glucose uptake. Visfatin stimulated glucose uptake in differentiated skeletal muscle cells. However, inhibition of AMPKα2 with an inhibitor or with knockdown of AMPKα2 using siRNA blocked visfatin-induced glucose uptake, which indicates that visfatin stimulates glucose uptake through the AMPKα2 pathway. Visfatin increased the intracellular Ca(2) (+) concentration. STO-609, a calmodulin-dependent protein kinase kinase inhibitor, blocked visfatin-induced AMPK phosphorylation and glucose uptake. Visfatin-mediated activation of p38 MAPK was AMPKα2-dependent. Furthermore, both inhibition and knockdown of p38 MAPK blocked visfatin-induced glucose uptake. Visfatin increased glucose transporter type 4 (GLUT4) mRNA and protein levels. In addition, visfatin stimulated the translocation of GLUT4 to the plasma membrane, and this effect was suppressed by AMPKα2 inhibition. The present results indicate that visfatin plays an important role in glucose metabolism via the Ca(2) (+)-mediated AMPK-p38 MAPK pathway.
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Joong Kwan
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Hyung Ip
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, Korea anatomykim@korea.ac.kr.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D020013:Calcium Signaling; D002460:Cell Line; D016207:Cytokines / Q000502:physiology*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; C534978:Prkaa2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose
keywords: AMPK; adipokine; calcium; diabetes; glucose transport