title: AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes.
abstract: 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-α production.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Wu
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Huang
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Huang
authors.forename: Jer-An
authors.initials: JA
authors.lastname: Lin
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D015398:Signal Transduction
chemical_list: D017127:Glycation End Products, Advanced; D007328:Insulin; D005947:Glucose