Isorhapontigenin Improves Diabetes in Mice via Regulating the Activity and Stability of PPARγ in Adipocytes
Isorhapontigenin Improves Diabetes in Mice via Regulating the Activity and Stability of PPARγ in Adipocytes
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DOI：
10.1021/acs.jafc.0c00515
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发表时间：
2020-04-01
影响因子：
6.1
通讯作者：
Wu, Jiang Wei
中科院分区：
文献类型：
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作者：
Chu, Xin Yi;Yang, Shi Zhen;Wu, Jiang Wei
异橙皮素是一种从多种植物和水果中分离出来的天然生物活性二苯乙烯。据报道，它在体外和实验动物模型中表现出多种生理活性，包括抗癌和抗炎症活性。本研究旨在探讨异橙皮素在体内是否具有抗糖尿病作用。为此，糖尿病db/db小鼠分别腹腔注射25 mg kg（-1）异橙皮抗原原或对照物，持续5周。结果表明，异橙皮素治疗显著降低餐后血糖、胰岛素和游离脂肪酸水平，这是糖尿病的三种标志物。进一步的研究表明，ITT和GTT显示异橙皮素治疗可显著改善db/db小鼠的胰岛素敏感性和葡萄糖耐量。综上所述，这些生理结果表明异橙皮素在体内具有抗糖尿病的特性。从机制上讲，异橙皮素介导的抗糖尿病作用是由脂肪组织的有利变化引起的，包括脂肪细胞直径的减少和脂肪胰岛素敏感性的改善。对3T3-L1细胞的进一步研究表明，异脂降原素处理通过上调主要脂肪生成调节因子PPAR的活性来促进前脂肪细胞分化。以及蛋白酶体降解的减速。总之，我们的研究结果首次确立了异橙皮素作为潜在的糖尿病治疗营养剂的重要作用。
Isorhapontigenin is a natural bioactive stilbene isolated from various plants and fruits. It has been reported to exhibit several physiological activities including anticancer and anti-inflammation activity in vitro and in experimental animal models. This study aimed to investigate whether isorhapontigenin exerts antidiabetic effects in vivo. To this end, diabetic db/db mice were treated with either 25 mg kg(-1) of isorhapontigenin or vehicle intraperitoneally for a period of 5 weeks. The results show that isorhapontigenin treatment significantly reduced postprandial levels of glucose, insulin, as well as free fatty acid, three markers of diabetes. Further studies show that isorhapontigenin treatment markedly improves insulin sensitivity and glucose tolerance of db/db mice as shown by ITT and GTT. Together, these physiological results show that isorhapontigenin possesses antidiabetic properties in vivo. Mechanistically, the isorhapontigenin-mediated antidiabetic effect is caused by favorable changes in adipose tissue, including reductions in adipocyte diameter and improved adipose insulin sensitivity. Further studies with 3T3-L1 cells show that isorhapontigenin treatment promotes preadipocyte differentiation by upregulation of the activity of the master adipogenic regulator PPAR. and deceleration of its proteasomal degradation. Together, our results establish for the first time an important role of isorhapontigenin as a potential nutraceutical agent for diabetes treatment.