Open AccessRole of insulin receptor substrate‐1 for diethylnitrosamine plus high‐fat diet‐induced hepatic tumorigenesis in mice
Author(s) -
Zolzaya Khadbaatar,
Nakamura Akinobu,
Tajima Kazuki,
Terauchi Yasuo
Publication year - 2014
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12128
Subject(s) - irs1 , endocrinology , medicine , carcinogenesis , insulin , knockout mouse , insulin receptor , triglyceride , intraperitoneal injection , diabetes mellitus , receptor , insulin resistance , cholesterol , cancer
We investigated the role of insulin receptor substrate ( I rs)‐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.