双乙酰丙酮氧钒化合物通过降低激素敏感酯酶和脂滴包被蛋白的磷酸化水平抑制具胰岛素抵抗的3T3-L1脂肪细胞在异丙肾上腺素刺激下的脂肪分解

doi:10.5246/jcps.2016.11.090

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (11): 814-820.DOI: 10.5246/jcps.2016.11.090

双乙酰丙酮氧钒化合物通过降低激素敏感酯酶和脂滴包被蛋白的磷酸化水平抑制具胰岛素抵抗的3T3-L1脂肪细胞在异丙肾上腺素刺激下的脂肪分解

胡霞, 刘竟成, 于游, 卞卫霞, 杨晓改^*

北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2016-05-13 修回日期:2016-07-25 出版日期:2016-11-26 发布日期:2016-08-10
通讯作者: Tel.: +86-010-82805956, E-mail: yxg@bjmu.edu.cn
基金资助:
This work was supported by National Natural Science Foundation of China (Grant No. 21171011 and 21671009).

Bis(acetylacetonato)-oxidovanadium(IV) inhibits isoproterenol-induced lipolysis in insulin-resistant 3T3-L1 adipocytes by reducing phosphorylation of perilipin and hormone-sensitive lipase

Xia Hu, Jingcheng Liu, You Yu, Weixia Bian, Xiaogai Yang^*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2016-05-13 Revised:2016-07-25 Online:2016-11-26 Published:2016-08-10
Contact: Tel.: +86-010-82805956, E-mail: yxg@bjmu.edu.cn
Supported by:
This work was supported by National Natural Science Foundation of China (Grant No. 21171011 and 21671009).

摘要/Abstract

摘要：

胰岛素抵抗是二型糖尿病的关键病理特征之一, 而脂代谢紊乱在二型糖尿病中也普遍存在。尽管基于其类胰岛素效应, 多种钒化合物被作为潜在的抗糖尿病药物进行研究, 但很少有研究涉及其抑制脂解的效应及机制。本工作用高糖和高胰岛素共同刺激分化成熟的3T3-L1脂肪细胞使其形成胰岛素抵抗状态, 来模拟II型糖尿病的病理状态, 并用油红O染色以及在胰岛素处理下Akt, AS160和GSK3的磷酸化水平下降作为模型的确认指标。结果表明, 在正常和胰岛素抵抗的状态下, VO(acac)₂都可以通过降低激素敏感酯酶(HSL)和脂滴包被蛋白(perilipin)的磷酸化水平而抑制异丙肾上腺素诱导的脂解。此外, 研究还显示, 尽管VO(acac)₂对Akt的激活程度相对于对照胰岛素敏感的脂肪细胞显著降低时, 它对脂解的抑制率也并未降低, 这提示此化合物在胰岛素抵抗状态还可通过Akt非依赖的路径抑制PKA的活性。本研究将有助于阐明钒化合物的抗糖尿病机制及钒化合物的应用前景; 同时也可为抗糖尿病药物的筛选提供一个有用的模型。

关键词: 双乙酰丙酮氧钒, 脂肪分解, 胰岛素抵抗3T3-L1脂肪细胞

Abstract:

Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus (T2DM), and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis(acetylacetonato)-oxidovanadium (IV) (VO(acac)₂) could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO(acac)₂ were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO(acac)₂ might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.

Key words: Bis(acetylacetonato)-oxidovanadium (IV), Lipolysis, Insulin-resistant 3T3-L1 adipocytes

中图分类号:

R977.15

Supporting:

胡霞, 刘竟成, 于游, 卞卫霞, 杨晓改. 双乙酰丙酮氧钒化合物通过降低激素敏感酯酶和脂滴包被蛋白的磷酸化水平抑制具胰岛素抵抗的3T3-L1脂肪细胞在异丙肾上腺素刺激下的脂肪分解[J]. 中国药学(英文版), 2016, 25(11): 814-820.

Xia Hu, Jingcheng Liu, You Yu, Weixia Bian, Xiaogai Yang. Bis(acetylacetonato)-oxidovanadium(IV) inhibits isoproterenol-induced lipolysis in insulin-resistant 3T3-L1 adipocytes by reducing phosphorylation of perilipin and hormone-sensitive lipase[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(11): 814-820.

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双乙酰丙酮氧钒化合物通过降低激素敏感酯酶和脂滴包被蛋白的磷酸化水平抑制具胰岛素抵抗的3T3-L1脂肪细胞在异丙肾上腺素刺激下的脂肪分解

Bis(acetylacetonato)-oxidovanadium(IV) inhibits isoproterenol-induced lipolysis in insulin-resistant 3T3-L1 adipocytes by reducing phosphorylation of perilipin and hormone-sensitive lipase

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