Paeonol Ameliorates Glucose and Lipid Metabolism in Experimental Diabetes by Activating Akt
Paeonol Ameliorates Glucose and Lipid Metabolism in Experimental Diabetes by Activating Akt
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丹皮酚通过激活 Akt 改善实验性糖尿病中的葡萄糖和脂质代谢
DOI：
10.3389/fphar.2019.00261
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Heqing Huang
中科院分区：
文献类型：
--
作者：
Futian Xu;Haiming Xiao;Renbin Liu;Yan Yang;Meng Zhang;Lihao Chen;Zhiquan Chen;Peiqing Liu;Heqing Huang
我们先前的研究证明，丹皮酚(Pae)可以降低糖尿病小鼠的血糖水平。也有一些关于它可能用于糖尿病治疗的报道。然而，Pae在糖尿病中调节糖脂代谢的作用在很大程度上仍不清楚。考虑到丝氨酸/苏氨酸激酶B(Akt)在糖脂代谢中的重要作用，我们探讨了Pae是否能通过Akt改善糖脂代谢紊乱。在这里，我们发现Pae能降低糖尿病小鼠的空腹血糖、糖化血清蛋白、血清胆固醇和甘油三酯(TG)、肝糖原、胆固醇和TG。此外，Pae还可增强葡萄糖激酶(GCK)和低密度脂蛋白受体(LDLR)蛋白的表达，并增加Akt的磷酸化。在胰岛素抵抗的HepG2细胞中，PAE增加了葡萄糖的摄取，减少了脂肪的积累。更重要的是，PAE提高了LDLR和GCK的表达以及Akt的磷酸化，这与体内的结果一致。Akt基因敲除和抑制实验表明，Pae通过激活Akt来调节LDLR和GCK的表达。分子对接实验表明，PAE与Akt2之间形成了稳定的氢键。以上实验表明，Pae可改善糖脂代谢紊乱，其机制与激活Akt密切相关。
Our previous study proved that paeonol (Pae) could lower blood glucose levels of diabetic mice. There are also a few reports of its potential use for diabetes treatment. However, the role of Pae in regulating glucose and lipid metabolism in diabetes remains largely unknown. Considering the critical role of serine/threonine kinase B (Akt) in glucose and lipid metabolism, we explored whether Pae could improve glucose and lipid metabolism disorders via Akt. Here, we found that Pae attenuated fasting blood glucose, glycosylated serum protein, serum cholesterol and triglyceride (TG), hepatic glycogen, cholesterol and TG in diabetic mice. Moreover, Pae enhanced glucokinase (GCK) and low-density lipoprotein receptor (LDLR) protein expressions, and increased the phosphorylation of Akt. In insulin-resistant HepG2 cells, Pae increased glucose uptake and decreased lipid accumulation. What’s more, Pae elevated LDLR and GCK expressions as well as Akt phosphorylation, which was consistent with the in vivo results. Knockdown and inhibition experiments of Akt revealed that Pae regulated LDLR and GCK expressions through activation of Akt. Finally, molecular docking assay indicated the steady hydrogen bond was formed between Pae and Akt2. Experiments above suggested that Pae ameliorated glucose and lipid metabolism disorders and the underlying mechanism was closely related to the activation of Akt.
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影响因子：
29
作者：
Lin HV;Accili D
通讯作者：
Accili D
影响因子：
29
作者：
Yecies JL;Zhang HH;Menon S;Liu S;Yecies D;Lipovsky AI;Gorgun C;Kwiatkowski DJ;Hotamisligil GS;Lee CH;Manning BD
通讯作者：
Manning BD
DOI：
10.1002/14651858.cd002966.pub4
发表时间：
2015-09
期刊：
The Cochrane database of systematic reviews
影响因子：
--
作者：
A. Sáenz;Inmaculada Fernandez-Esteban;Á. Mataix;Monica Ausejo Segura;Marta Roqué i Figuls;D. Moher
通讯作者：
A. Sáenz;Inmaculada Fernandez-Esteban;Á. Mataix;Monica Ausejo Segura;Marta Roqué i Figuls;D. Moher
Akt 特异性激活剂 SC79 可预防蛛网膜下腔出血后的早期脑损伤。
DOI：
10.1021/acschemneuro.5b00306
发表时间：
2016
期刊：
ACS Chem Neurosci
影响因子：
--
作者：
Zhang Ding-Ding;Zhang Hua-Sheng;Hao Shuang-Ying;Yan Hui-Ying;Zhang Zi-Huan;Hu Yang-Chun;Zhuang Zong;Li Wei;Zhou Meng-Liang;Li Kuan-Yu;Hang Chun-Hua
通讯作者：
Hang Chun-Hua
影响因子：
7.7
作者：
Matveyenko AV;Liuwantara D;Gurlo T;Kirakossian D;Dalla Man C;Cobelli C;White MF;Copps KD;Volpi E;Fujita S;Butler PC
通讯作者：
Butler PC