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Ligustilide alleviates the insulin resistance, lipid accumulation, and pathological injury with elevated phosphorylated AMPK level in rats with diabetes mellitus
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-07-09 , DOI: 10.1080/10799893.2020.1789877
Sujuan Guo 1 , Guofeng Wang 1 , Zhengxiong Yang 1
Affiliation  

Abstract Background Diabetes mellitus (DM) is one of the major risk factors of disability and death worldwide. Despite of the protective role of ligustilide (LIG) in many cell types, we aimed to investigate whether LIG could be a potential to treat DM. Methods Sprague Dawley rats were randomly assigned to five groups. Rats except control were raised on a high-fat diet (HFD). Streptozotocin was intraperitoneally injected into HFD-fed rats to construct DM model. Rats in the LIG intervention groups received intraperitoneal injection of LIG (10, 20, and 40 mg/kg) post-induction of DM. Blood glucose, plasma insulin (p-insulin), adiponectin, HbA1C%, obesity index, HOMA-IR, and biochemical parameters were estimated. Histopathological analysis and apoptosis in liver and kidney, along with proliferation and apoptosis of islet β-cells, were analyzed. Expression of CPT-1 and ACC, and phosphorylation of Nrf2 and AMPKα1, were finally assessed. Results DM-induced alterations were all relived by LIG intervention. In brief, obesity index, glucose level, P-insulin content, HbA1C, and HOMA-IR were lowered while adiponectin level was elevated. Meanwhile, levels of TC, TG, ALT, and AST were decreased in the LIG intervention groups, along with up-regulated CPT-1 level and down-regulated ACC level. Pathological changes in liver and kidney tissues were alleviated, and apoptotic cells were reduced by LIG treatment. For islet β-cells, LIG up-regulated Ki67 and c-Myc expression, and mitigated ratios of Bax/Bcl-2 and cleaved cas3(9)/cas3(9). Finally, LIG could promote phosphorylation of Nrf2 and AMPKα1. Conclusions LIG alleviated the insulin resistance, lipid accumulation, and pathological injury with the activation of AMPK pathway in DM rats.

中文翻译:

川芎内酯通过升高的磷酸化 AMPK 水平减轻糖尿病大鼠的胰岛素抵抗、脂质积累和病理损伤

摘要 背景糖尿病(DM)是全球致残和死亡的主要危险因素之一。尽管川芎内酯 (LIG) 在许多细胞类型中具有保护作用,但我们的目标是研究 LIG 是否具有治疗 DM 的潜力。方法 Sprague Dawley 大鼠随机分为五组。除对照外的大鼠均采用高脂肪饮食 (HFD) 饲养。将链脲佐菌素腹腔注射到HFD喂养的大鼠中以构建DM模型。LIG 干预组的大鼠在诱导 DM 后接受腹腔注射 LIG(10、20 和 40 mg/kg)。估计了血糖、血浆胰岛素(p-胰岛素)、脂联素、HbA1C%、肥胖指数、HOMA-IR 和生化参数。分析了肝脏和肾脏的组织病理学分析和细胞凋亡,以及胰岛 β 细胞的增殖和凋亡。最后评估 CPT-1 和 ACC 的表达以及 Nrf2 和 AMPKα1 的磷酸化。结果 DM 诱导的改变全部通过 LIG 干预重现。简而言之,肥胖指数、葡萄糖水平、P-胰岛素含量、HbA1C 和 HOMA-IR 降低,而脂联素水平升高。同时,LIG干预组TC、TG、ALT和AST水平降低,CPT-1水平上调,ACC水平下调。LIG治疗减轻了肝肾组织的病理变化,减少了凋亡细胞。对于胰岛 β 细胞,LIG 上调 Ki67 和 c-Myc 的表达,并降低 Bax/Bcl-2 和裂解的 cas3(9)/cas3(9) 的比率。最后,LIG 可以促进 Nrf2 和 AMPKα1 的磷酸化。结论 LIG 减轻了胰岛素抵抗、脂质积累、
更新日期:2020-07-09
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