Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Life Sci. 2022 Jul 15;301:120633. doi: 10.1016/j.lfs.2022.120633. Epub 2022 May 12.
Cafeteria diet (CAF) is a well-established model used to mimic what occurs in human upon eating junk and ultra-processed food. This study aimed to investigate the possible protective impact of empagliflozin (EMPA) against CAF-induced insulin resistance (IR) in rats and the possible underlying mechanisms.
Rats were fed on CAF diet for 12 weeks while treatment with EMPA (10 & 30 mg/kg/day, orally) and/or metformin (MET) (100 mg/kg/day, orally) started at day 29.
Oral administration of EMPA and/or MET significantly and dose-dependently succeeded to attenuate CAF-induced obesity which was evidenced by decreased oral glucose tolerance test (AUC), insulin tolerance test (AUC) and decreased fasting serum insulin level besides improving the histopathological alterations induced by CAF. Moreover, EMPA significantly mitigated CAF-induced elevation in serum levels of creatinine urea, transaminases (ALT and AST), and increased albumin level as well as improving dyslipidemia and oxidative stress. Furthermore, EMPA markedly reduced renal levels of high mobility group box 1 (HMGB-1), toll like receptor4 (TLR-4) and nuclear factor κB (NF-κB) as well as decreasing the expression of tumor necrosis factor α (TNF-α) and Caspase 3. Combining EMPA with MET synergistically improved dyslipidemia, oxidative stress and enhanced kidney function.
EMPA administration could confer protection against CAF-induced IR and its complications through its hypoglycemic, insulin-sensitizing, hypolipidemic, hepatoprotective, renoprotective, anti-inflammatory, anti-oxidant and anti-apoptotic properties. Also, our findings highlighted the synergistic effect of combining EMPA with MET so this combination might be promising in treatment of IR.
自助餐厅饮食（CAF）是一种成熟的模型，用于模拟人类食用垃圾和超加工食品时的情况。本研究旨在探讨依帕列净（EMPA）对 CAF 诱导的大鼠胰岛素抵抗（IR）的可能保护作用及其潜在机制。
大鼠给予 CAF 饮食 12 周，同时从第 29 天开始给予 EMPA（10 和 30mg/kg/天，口服）和/或二甲双胍（MET）（100mg/kg/天，口服）治疗。
EMPA 和/或 MET 的口服给药显著且呈剂量依赖性地减轻 CAF 诱导的肥胖，这表现在口服葡萄糖耐量试验（AUC）、胰岛素耐量试验（AUC）和空腹血清胰岛素水平降低，同时改善 CAF 引起的组织病理学改变。此外，EMPA 显著减轻 CAF 诱导的血清肌酐、尿素、转氨酶（ALT 和 AST）水平升高和白蛋白水平升高，以及改善血脂异常和氧化应激。此外，EMPA 显著降低肾脏高迁移率族蛋白 1（HMGB-1）、Toll 样受体 4（TLR-4）和核因子 κB（NF-κB）水平，并降低肿瘤坏死因子 α（TNF-α）和 Caspase 3 的表达。EMPA 与 MET 联合使用可协同改善血脂异常、氧化应激和增强肾功能。
EMPA 的给药可通过其降血糖、胰岛素增敏、调脂、保肝、护肾、抗炎、抗氧化和抗细胞凋亡作用，为 CAF 诱导的 IR 及其并发症提供保护。此外，我们的研究结果强调了 EMPA 与 MET 联合使用的协同效应，因此这种联合治疗可能对 IR 的治疗有前景。
