Liver fibrosis is a common complication of diabetes mellitus, with a major global public health concern. Linagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), is classically used to treat type 2 diabetes mellitus and improves insulin resistance. Additional potential influences of linagliptin on liver fibrosis are still unclear. The present study was undertaken to investigate the therapeutic credit of linagliptin in hepatic fibrosis induced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Moreover, the mechanisms underline its anti-fibrotic effect were explored. To induce liver fibrosis with T2DM; male Sprague-Dawley albino rats were fed on a high-fat high-sucrose diet for 28 days then exposed to a single dose of STZ (30 mg/kg, IP). After two days of STZ injection, a diabetes confirmation test was done and all diabetic rats were constantly fed on HFD for thirty days with or without treatment with linagliptin (6 mg/kg). Hepatotoxicity markers, lipid profile screening, insulin signaling, inflammatory cytokines (TNF-α, IL-6, NF-κB p65), fibrosis markers (Collagen, α-SMA, TGF-β1) and histopathological studies including hematoxylin and eosin (H&E) as well Masson's trichrome stains were performed. In our preliminary study, linagliptin at a dose of 6 mg/kg was chosen as the optimum anti-diabetic dose in rats challenged with STZ. Linagliptin significantly improved insulin sensitivity and lipid profile and reduced inflammatory mediators, and collagen depositions in rats with liver fibrosis and T2DM. In conclusion, above and beyond its anti-diabetic effect, this study introduced linagliptin as a promising option for preventing the pathological progression of liver fibrosis associated with T2DM.

肝纤维化是糖尿病的常见并发症，主要涉及全球公共卫生。利格列汀是一种二肽基肽酶4抑制剂（DPP-4），通常用于治疗2型糖尿病并改善胰岛素抵抗。利格列汀对肝纤维化的其他潜在影响仍不清楚。本研究旨在研究利格列汀在高脂饮食（HFD）和链脲佐菌素（STZ）诱导的肝纤维化中的治疗作用。此外，探索了强调其抗纤维化作用的机制。用T2DM诱导肝纤维化；用高脂高蔗糖饮食喂养雄性Sprague-Dawley白化病大鼠28天，然后暴露于单剂量的STZ（30 mg / kg，IP）。注射STZ两天后，进行了糖尿病确证试验，所有糖尿病大鼠在接受或未接受利拉列汀（6 mg / kg）治疗的情况下均持续接受HFD喂养30天。肝毒性标志物，脂质分布筛查，胰岛素信号传导，炎性细胞因子（TNF-α，IL-6，NF-κBp65），纤维化标志物（胶原，α-SMA，TGF-β1）以及包括苏木精和曙红（H＆E）在内的组织病理学研究以及进行了Masson的三色染色。在我们的初步研究中，选择6mg / kg的利拉列汀作为STZ攻击大鼠的最佳抗糖尿病剂量。利格列汀可以显着改善胰岛素敏感性和脂质分布，并减少患有肝纤维化和T2DM的大鼠的炎症介质和胶原蛋白沉积。总之，除了抗糖尿病作用外，