ER Stress Amelioration by Saxagliptin Protects the Liver Against Fructose-induced Insulin Resistance

Abstract

The study is aimed to demonstrate whether saxagliptin treatment may reduce endoplasmic reticulum (ER) stress, oxidative damage, and inflammation in the liver of fructose-induced insulin resistance (IR) rats. Twenty-eight rats were divided as control, IR, saxagliptin treatment (ST) and IR+ST groups. IR caused by fructose (10%) administration for 10weeks and, ST was administered for 15d. The liver tissues were obtained from rats. ER stress markers were analyzed using Real-Time PCR. Oxidative stress was measured. The inflammation in the liver was detected by the streptavidin-biotin immunostaining method. The values of total oxidant/antioxidant status were the same between control and IR rats. The numbers of IL-6, NF-κB and PPARγ immune+ cells showed significant changes in the liver among four groups. The increased mRNA expression levels of ER stress and apoptosis markers as GRP78, PERK, IRE1α, ATF-4 and -6, CHOP, Caspase-3, -8, -9 and -12 in IR reduced with ST. These findings indicate that saxagliptin treatment may ameliorate IR by reducing ER stress rather than inflammation and oxidative stress in the liver.