AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes

Chi Hao Wu, Hsiao Wen Huang, Shang Ming Huang, Jer An Lin, Chi-Tai Yeh, Gow Chin Yen

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7978-7984
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume59
Issue number14
DOIs
Publication statusPublished - Jul 27 2011

Keywords

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

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

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