Effect of Iron-Mediated Oxidative Stress on Insulin Resistance Through the Forkhead Box-Containing Protein O Subfamily-1 (FOXO-1) Pathway in Chronic Hepatitis C.docVIP

International Journal of Clinical Medicine, 2013, 4, 10-18 /10.4236/ijcm.2013.41004 Published Online January 2013 (/journal/ijcm) Effect of Iron-Mediated Oxidative Stress on Insulin Resistance through the Forkhead Box-Containing Protein O Subfamily-1 (FOXO-1) Pathway in Chronic Hepatitis C* Yoshinao Kobayashi Rumi Mifuji-Moroka , Motoh Iwasa , Hirohide Miyachi , Ryosuke Sugimoto , Hideaki Tanaka , 1,2# 2 2 2 2 2 2 1 2 , Naoki Fujita , Yasuhiro Sumida , Yoshiyuki Takei 1 2 Center for Physical and Mental Health, Mie University Graduate School of Medicine, Tsu, Japan; Department of Gastroenterology and Hepatology, Mie University Graduate school of Medicine, Tsu, Japan. # Email: yoshinao@hac.mie-u.ac.jp Received November 6 , 2012; revised December 12 , 2012; accepted January 25 , 2013 th th th ABSTRACT Aims: Chronic hepatitis C virus (HCV) infection is often associated with glucose metabolic disorders and iron overload. It has recently been shown that reactive oxygen species (ROS) increase gluconeogenesis in hepatocytes through the forkhead box-containing protein O subfamily-1 (FOXO1)-dependent pathway. The aim of this study is proving a cause- and-effect relationship between iron-mediated ROS production and insulin resistance (IR) in chronic hepatitis C (CH-C) patients. Methods: The study included 42 patients with CH-C (22 males and 20 females, median age 53 years). Homeo- stasis model assessment of insulin resistance (HOMA-IR) value was assessed for each patient at entry. Gene expression levels in the bio