期刊
LIFE SCIENCES
卷 93, 期 5-6, 页码 240-246出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2013.06.014
关键词
Diacylglycerol; Protein kinase C; GLUT4; Trafficking
Aim: Emerging evidence has pointed to the participation of protein kinase C (PKC) in insulin-regulated trafficking of the glucose transporter GLUT4. The present study investigated the effect of the PKC activator diacylglycerol (DAG) on GLUT4 trafficking and glucose uptake. Main methods: 3T3L1-GLUT4myc fibroblast cells expressing GLUT4myc were differentiated into adipocytes. Western blotting, glucose assay, and real-time RT-PCR were carried out in 3T3L1-GLUT4myc adipocytes. PKC lambda/iota, -zeta, -epsilon, and -gamma were knocked-down by transfecting each siRNA. Activity of PKC isozymes was assayed under the cell-free conditions. Key findings: Insulin increased cell surface localization of GLUT4 in 3T3L1-GLUT4myc adipocytes, and a similar effect was obtained with 1,2-dioleoyl-sn-glycerol (DO-DAG), 1-oleoyl-2-acetyl-sn-glycerol (OA-DAG), or 1,2-dipalmitoyl-sn-glycerol (DP-DAG). Like insulin, DO-DAG stimulated glucose uptake into adipocytes, but no significant synergistic increase in the glucose uptake was found with co-treatment with insulin and DO-DAG. Insulin activated Akt in adipocytes, but no Akt activation was induced by any investigated DAG. In the cell-free PKC assay, DAGs examined here activated PKC alpha, -beta I, -beta II, -delta, and -epsilon, but the atypical PKC isozymes PKC lambda/iota, and were not activated. Insulin-induced GLUT4 translocation to the cell surface was inhibited by knocking-down PKCXA, and but not PKC gamma or -epsilon. In contrast, DO-DAG-induced GLUT4 translocation to the cell surface was clearly prevented by knocking-down PKC epsilon. Significance: The results of the present study indicate that DAG stimulates GLUT4 translocation to the cell surface by activating PKC epsilon, regardless of PKC lambda/-iota, and -zeta. (C) 2013 Elsevier Inc. All rights reserved.
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