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

Abstract

Background/Aim. 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. Material and Methods. Twenty-eight rats were divided as control, IR, saxagliptin treatment (ST) and IR+ST groups. IR caused by fructose (10%) administration for 10 weeks and, ST was administered for 15 d. 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. Results. the values of total oxidant/antioxidant status were the same between control and IR rats. the numbers of IL-6, NF-kappa B and PPAR gamma 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, IRE1 alpha, ATF-4 and -6, CHOP, Caspase-3, -8, -9 and -12 in IR reduced with ST. Conclusion. These findings indicate that saxagliptin treatment may ameliorate IR by reducing ER stress rather than inflammation and oxidative stress in the liver. (C) 2020 IMSS. Published by Elsevier Inc.