叔丁基对苯二酚可缓解糖尿病引起的胰岛素抵抗和肝脂肪变性。
Tert-Butylhydroquinone alleviates insulin resistance and liver steatosis in diabetes.
机构信息
Department of Clinical Pharmacy, College of Pharmacy, Xinxiang Medical University; Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention; Xinxiang Key, Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Xinxiang, China.
Department of Clinical Pharmacy, College of Pharmacy, Xinxiang Medical University; Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention; Xinxiang Key, Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development; Department of Pharmacy, Xinxiang Medical University First Affiliated Hospital, Xinxiang, China.
出版信息
Indian J Pharmacol. 2022 Mar-Apr;54(2):118-125. doi: 10.4103/ijp.ijp_440_21.
OBJECTIVES
This work aimed to determine tert-Butylhydroquinone (TBHQ)'s effects on insulin resistance (IR) and liver steatosis in diabetic animals and to explore the underpinning mechanisms.
MATERIALS AND METHODS
Male ApoEmice underwent streptozocin (STZ) administration while receiving a sucrose/fat-rich diet for type 2 diabetes mellitus (T2DM) establishment. This was followed by a 6-week TBHQ administration. Body weight, fasting (FBG) and postprandial (PBG) blood glucose amounts, and insulin concentrations were measured, and the oral glucose tolerance test (OGTT) was carried out. Hematoxylin and eosin (H and E) staining and immunoblot were carried out for assessing histology and protein amounts in the liver tissue samples. In addition, cultured HepG2 cells were administered HClO and insulin for IR induction, and immunoblot was carried out for protein evaluation. Finally, the cells were stained with the Hoechst dye for apoptosis evaluation.
RESULTS
The model animals showed T2DM signs, and TBHQ decreased FBG, ameliorated glucose tolerance and reduced liver steatosis in these animals. In addition, TBHQ markedly upregulated AMPKα2, GLUT4 and GSK3 β, as well as phosphorylated PI3K and AKT in the liver of mice with T2DM. In agreement, TBHQ decreased HClO-and insulin-related IR in cells and suppressed apoptosis through AMPKα2/PI3K/AKT signaling.
CONCLUSIONS
TBHQ alleviates IR and liver steatosis in a mouse model of T2DM likely through AMPKα2/PI3K/AKT signaling.
目的
本研究旨在探讨叔丁基对苯二酚（TBHQ）对糖尿病动物胰岛素抵抗（IR）和肝脂肪变性的作用，并探讨其潜在机制。
材料与方法
雄性载脂蛋白 E 基因敲除（ApoE-/-）小鼠接受链脲佐菌素（STZ）处理，并给予高蔗糖/高脂肪饮食以建立 2 型糖尿病（T2DM）模型。随后进行 6 周的 TBHQ 处理。测量体重、空腹（FBG）和餐后（PBG）血糖水平以及胰岛素浓度，并进行口服葡萄糖耐量试验（OGTT）。通过苏木精和伊红（H 和 E）染色和免疫印迹检测肝组织样本的组织学和蛋白含量。此外，培养 HepG2 细胞并用 HClO 和胰岛素诱导 IR，并用免疫印迹检测蛋白表达。最后，用 Hoechst 染料对细胞进行凋亡染色。
结果
模型动物表现出 T2DM 特征，TBHQ 降低了 FBG，改善了这些动物的葡萄糖耐量，并减轻了肝脂肪变性。此外，TBHQ 显著上调了 AMPKα2、GLUT4 和 GSK3β，以及糖尿病小鼠肝脏中磷酸化的 PI3K 和 AKT。一致地，TBHQ 降低了 HClO 和胰岛素诱导的细胞 IR，并通过 AMPKα2/PI3K/AKT 信号通路抑制了细胞凋亡。
结论
TBHQ 通过 AMPKα2/PI3K/AKT 信号通路缓解 T2DM 小鼠的 IR 和肝脂肪变性。
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