Mechanistic insights into the effects of quercetin and/or GLP-1 analogue liraglutide on high-fat diet/streptozotocin-induced type 2 diabetes in rats

Background: The development of complementary treatment strategies that focuses on achieving a balance between adaptive and apoptotic unfolded protein response (UPR), enhancing endoplasmic reticulum (ER) homeostasis, and thus preserving beta cell mass and function is particularly warranted. Aim: This study was designed to investigate the effectiveness of the combined treatment by Quercetin (QUE) and Liraglutide (LIRA) in modulating hyperglycemia, insulin-insensitivity, UPR/ER stress markers, apoptosis, oxidative stress and inflammation using a high-fat diet/streptozotocin-induced type 2 diabetic rat model. Methods: Sixty male albino rats were allocated into five equal groups: normal control, diabetic control, LIRA treated diabetic; QUE treated diabetic and combined treatment diabetic groups. Fasting glucose, insulin, CHOP, macrophage inflammatory protein -1 alpha (MIP-1 alpha) and Bax, Bcl(2) levels were estimated by ELISA; mRNA expression levels of the spliced X-box binding protein 1 (XBP1) were estimated using quantitative real-time RT-PCR, while MDA, advanced oxidation protein products, reduced glutathione levels and protein disulfide isomerase (PDI) activity were evaluated spectrophotometrically. Pancreatic tissues were also subjected to histopathological examination. Results: The combined treatment with both LIRA and QUE causes significant improvements in all the studied parameters; including XBP1 splicing, CHOP, MIP-1 alpha, Bax/Bcl(2) ratio, PDI activity, as well as oxidative stress markers as compared to either treatment alone. It also attenuated pancreatic histopathological damage. In conclusion: Our study nominates this combination to be used in T2DM to achieve adequate glycaemic control and to preserve optimal b cell function. (C) 2017 Published by Elsevier Masson SAS.