Abstract:

OBJECTIVE: Insulin resistance (IR) is a major characteristic of type 2 diabetes millitus which is difficult to be prevented and treated, and its pathogenesis is still uncertain. The aim of this study was to investigate the change of oxidative stress and nuclear-mitochondria axis in hepatic tissue during the process of insulin resistance induced by high-fat-diet in mice. METHODS:Male C57 mice were randomly divided into 2 groups, the mice in control group were fed with normal chow while those in high fat diet group were fed with 10% lard oil containing diet to induce insulin resistance. The hepatic reactive oxygen species level, malondialdehyde (MDA) content and lipid accumulation were tested. P-Akt, Nrf2, NRF-1 and mtTFA expression in liver tissue were determined by Western blot. RESULTS:Compared with controls, mice fed with a high fat diet could induce insulin resistance. During this process, hepatic fat and ROS accumulation were both increased, the MDA content was also elevated by about 30%. The expression of insulin signal transduction protein P-Akt was attenuated by 45% whilst the expressions of Nrf2, NRF-1 and mtTFA were decreased by 20%-30%. CONCLUSION:Oxidative stress and dysfunction of Nrf2/NRF-1/mtTFA axis may play important roles in the development of insulin resistance induced by a high fat diet.

Key words: insulin resistance, oxidative stress, Nrf2, NRF-1, mtTFA