Chronic insulin treatment causes insulin resistance in 3T3-L1 adipocytes through oxidative stress

Xuemei Ge, Qiujing Yu, Wei Qi, Xianglin Shi, Qiwei Zhai

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Insulin resistance and hyperinsulinemia are commonly present in obesity and pre-diabetes, and hyperinsulinemia is both a marker and a cause for insulin resistance. However, the molecular link between hyperinsulinemia and insulin resistance remains elusive. The present study examined the effect of chronic insulin treatment on the reactive oxygen species (ROS) production, insulin signalling and insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The results showed that chronic insulin treatment significantly increased the intracellular generation of superoxide anion, hydrogen peroxide and hydroxyl radical. ROS induced by chronic insulin treatment inhibited insulin signalling and glucose uptake, induced endoplasmic reticulum (ER) stress and JNK activation. Furthermore, these effects were reversed by antioxidants N-acetylcysteine, superoxide dismutase or catalase. These results suggested that ROS, ER stress and JNK pathway are involved in insulin resistance induced by chronic insulin treatment. Therefore, oxidative stress could be a potential interventional target for hyperinsulinemia-induced insulin resistance and related diseases.

Original languageEnglish
Pages (from-to)582-591
Number of pages10
JournalFree Radical Research
Volume42
Issue number6
DOIs
StatePublished - Jun 2008

Bibliographical note

Funding Information:
This study was supported by grants from National Natural Science Foundation of China (30570558, 30671775 and 30271124), the Chinese Academy of Sciences (KSCX2-YW-N-034 and KSCX1-YW-02), National Basic Research Program of China (973 Program, 2006CB503900 and 2007CB914501), the Science and Technology Commission of Shanghai Municipality (06DZ19021), PLA (02M003) and the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences (2007KIP103). Q. Zhai is a scholar of the Hundred Talents Program from Chinese Academy of Sciences.

Keywords

  • Diabetes
  • ER stress
  • Insulin resistance
  • JNK
  • ROS

ASJC Scopus subject areas

  • Biochemistry

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