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黄芪甲苷通过促进 AMPK/mTOR 介导的自噬减轻 2 型糖尿病肝损伤。

Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR‑mediated autophagy.

机构信息

Key Laboratory of Anti‑Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.

出版信息

Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12076. Epub 2021 Apr 13.

Abstract

Diabetic liver injury is a serious complication of type 2 diabetes mellitus (T2DM), which is often irreversible in the later stage, and affects the quality of life. Autophagy serves an important role in the occurrence and development of diabetic liver injury. For example, it can improve insulin resistance (IR), dyslipidaemia, oxidative stress and inflammation. Astragaloside IV (AS‑IV) is a natural saponin isolated from the plant , which has comprehensive pharmacological effects, such as anti‑oxidation, anti‑inflammation and anti‑apoptosis properties, as well as can enhance immunity. However, whether AS‑IV can alleviate diabetic liver injury in T2DM and its underlying mechanisms remain unknown. The present study used high‑fat diets combined with low‑dose streptozotocin to induce a diabetic liver injury model in T2DM rats to investigate whether AS‑IV could alleviate diabetic liver injury and to identify its underlying mechanisms. The results demonstrated that AS‑IV treatment could restore changes in food intake, water intake, urine volume and body weight, as well as improve liver function and glucose homeostasis in T2DM rats. Moreover, AS‑IV treatment promoted suppressed autophagy in the liver of T2DM rats and improved IR, dyslipidaemia, oxidative stress and inflammation. In addition, AS‑IV activated adenosine monophosphate‑activated protein kinase (AMPK), which inhibited mTOR. Taken together, the present study suggested that AS‑IV alleviated diabetic liver injury in T2DM rats, and its mechanism may be associated with the promotion of AMPK/mTOR‑mediated autophagy, which further improved IR, dyslipidaemia, oxidative stress and inflammation. Thus, the regulation of autophagy may be an effective strategy to treat diabetic liver injury in T2DM.

摘要

糖尿病性肝损伤是 2 型糖尿病(T2DM)的一种严重并发症,在后期往往不可逆转,影响生活质量。自噬在糖尿病性肝损伤的发生和发展中起重要作用。例如,它可以改善胰岛素抵抗(IR)、血脂异常、氧化应激和炎症。黄芪甲苷(AS-IV)是从植物中分离得到的天然皂苷,具有广泛的药理作用,如抗氧化、抗炎和抗凋亡作用,以及增强免疫力。然而,AS-IV 是否可以缓解 T2DM 中的糖尿病性肝损伤及其潜在机制尚不清楚。本研究采用高脂饮食联合小剂量链脲佐菌素诱导 T2DM 大鼠糖尿病性肝损伤模型,探讨 AS-IV 是否可以缓解糖尿病性肝损伤及其潜在机制。结果表明,AS-IV 治疗可恢复 T2DM 大鼠的摄食、饮水、尿量和体重变化,改善肝功能和葡萄糖稳态。此外,AS-IV 治疗可促进 T2DM 大鼠肝脏中受抑制的自噬,并改善 IR、血脂异常、氧化应激和炎症。此外,AS-IV 激活了 AMP 激活的蛋白激酶(AMPK),从而抑制了 mTOR。综上所述,本研究表明 AS-IV 缓解了 T2DM 大鼠的糖尿病性肝损伤,其机制可能与促进 AMPK/mTOR 介导的自噬有关,进而改善 IR、血脂异常、氧化应激和炎症。因此,调节自噬可能是治疗 T2DM 中糖尿病性肝损伤的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd8e/8060804/b9cad6ec5b48/mmr-23-06-12076-g00.jpg

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