Asymmetric Dimethylarginine Impairs Glucose Utilization via ROS/TLR4 Pathway in Adipocytes: an Effect Prevented by Vitamin E

Autor: Xiao-Qing Zou, Kuan-Song Wang, Zhichun Yang, Yuan-Jian Li, Yan Wu, Yue-Yun Xiang, Xiao-Ping Chen
Rok vydání: 2009
Předmět:
Zdroj: Cellular Physiology and Biochemistry. 24:115-124
ISSN: 1421-9778
1015-8987
Popis: Asymmetric dimethylarginine (ADMA), the inhibitor of nitric oxide synthase (NOS), has been reported to be associated with glucose metabolism, but its mechanisms remain unknown.In 3T3-L1 adipocytes, we measured the effects of ADMA on glucose transport process under basal or insulin-induced condition, and examined the production of nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-alpha), and the expression of toll-like receptor 4 (TLR4).ADMA significantly impaired basal or insulin-stimulated 2-deoxy- [3H] glucose uptake, and decreased the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter-4 (GLUT4). Phosphorylated protein of IRS-1 and translocation of GLUT4 with insulin-stimulation were also inhibited by ADMA. NO decreased, while production of ROS and TNF-alpha, and expression of TLR4 increased after ADMA treatment. Vitamin E reduced the effects of ADMA on glucose transport system, and on NO, ROS and TLR4. Moreover, vitamin E decreased ADMA contents by up-regulating dimethylarginine dimethylaminohydrolase (DDAH) activity in adipocytes. Though L-arginine also increased NO level, but failed to reduce the effects of ADMA.ADMA significantly impairs both basal and insulin-stimulated glucose transport in adipocytes, which may relate to activation of the ROS/TLR4 pathway.
Databáze: OpenAIRE