Role of insulin receptor substrate‐1 for diethylnitrosamine plus high‐fat diet‐induced hepatic tumorigenesis in mice

Journal of Diabetes Investigation

Khadbaatar Zolzaya¹  Akinobu Nakamura¹  Kazuki Tajima¹ 

[1] Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

关键词: Diethylnitrosamine;    Hepatic tumorigenesis;    Insulin receptor substrate‐1;   

DOI  :  10.1111/jdi.12128

来源: Wiley

【 摘 要 】

Abstract

We investigated the role of insulin receptor substrate (Irs)-1 for diethylnitrosamine (DEN) plus high-fat (HF) diet-induced hepatic tumorigenesis in mice. We gave DEN by intraperitoneal injection at the dose of 80 mg/kg to 18-week-old wild-type (WT) and Irs1-knockout (Irs1^−/−) mice, which were fed a HF diet from 8 weeks-of-age until they were killed (52 weeks). The Irs1^−/− mice showed significantly lower plasma alanine aminotransferase levels, triglyceride contents in the liver and also lower expression levels of the genes encoding inflammatory cytokines than the WT mice. The incidence of DEN plus HF diet-induced hepatic tumors was 71.4% in the WT mice, whereas it was just 14.3% in the Irs1^−/− mice. The present study showed that Irs1 played an important role in DEN plus HF diet-induced hepatic tumorigenesis.

【 授权许可】

CC BY-NC   
© 2013 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd

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