AGE-Induced Interference of Glucose Uptake and Transport as a Possible Cause of Insulin Resistance in Adipocytes

作者：Wu Chi Hao; Huang Hsiao Wen; Huang Shang Ming; Lin Jer An; Yeh Chi Tai; Yen Gow Chin^*

来源：Journal of Agricultural and Food Chemistry, 2011, 59(14): 7978-7984.

DOI：10.1021/jf201271y

• adipocytes
• advanced glycation end products
• insulin resistance
• inflammation
• oxidative stress
• receptor for AGEs

The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h,p <0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-alpha production.

• 出版日期2011-7-27