Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice
Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice
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DOI：
10.1016/j.bcp.2010.01.034
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发表时间：
2010-06-01
影响因子：
5.8
通讯作者：
Woo, Je-Tae
中科院分区：
文献类型：
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作者：
Lee, Young-Sil;Cha, Byung-Yoon;Woo, Je-Tae
诺biletin是一种多甲氧基黄酮，存在于某些柑橘类水果中，具有多种药理作用，包括抗炎、抗肿瘤和神经保护特性。本研究探讨了降脂素对肥胖糖尿病ob/ob小鼠胰岛素敏感性的影响及其可能的机制。给予nobilletin （200 mg/kg）治疗ob/ob小鼠5周。诺比列素可显著改善血浆葡萄糖水平、稳态模型评估指标、口服糖耐量试验中的糖耐量和血浆脂联素水平。在白色脂肪组织（WAT）中，nobiletin显著降低炎症性脂肪因子如白细胞介素(IL)-6和单核细胞趋化蛋白(MCP)-1的mRNA表达水平，提高脂联素、过氧化物酶体增殖物激活受体(PPAR)- γ及其靶基因的mRNA表达水平。同时，nobiletin增加了WAT和肌肉中全质膜中葡萄糖转运蛋白（Glut） 4的表达水平，以及全细胞裂解物中Glut1和phospho-Akt的表达。诺比列素还增加了肌肉全细胞裂解物中Glut4蛋白的表达水平。综上所述，本研究结果表明，nobiletin通过调节WAT和肌肉中Glut1和Glut4的表达以及WAT中脂肪因子的表达，改善了肥胖糖尿病ob/ob小鼠的高血糖和胰岛素抵抗。(C) 2010爱思唯尔公司版权所有。
Nobiletin is a polymethoxylated flavone found in certain citrus fruits that exhibits various pharmacological effects including anti-inflammatory, antitumor and neuroprotective properties. The present study investigated the effects of nobiletin on insulin sensitivity in obese diabetic ob/ob mice, and the possible mechanisms involved. The ob/ob mice were treated with nobiletin (200 mg/kg) for 5 weeks. Nobiletin significantly improved the plasma glucose levels, homeostasis model assessment index, glucose tolerance in an oral glucose tolerance test and plasma adiponectin levels. In white adipose tissue (WAT), nobiletin significantly decreased the mRNA expression levels of inflammatory adipokines such as interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 and increased the mRNA expression levels of adiponectin, peroxisome proliferator-activated receptor (PPAR)-gamma and its target genes. At the same time, nobiletin increased the glucose transporter (Glut) 4 expression levels in the whole plasma membrane, and Glut1 and phospho-Akt expression in the whole cell lysates in WAT and muscle. Nobiletin also increased Glut4 protein expression level in the whole cell lysates of the muscle. Taken together, the present results suggest that nobiletin improved the hyperglycemia and insulin resistance in obese diabetic ob/ob mice by regulating expression of Glut1 and Glut4 in WAT and muscle, and expression of adipokines in WAT. (C) 2010 Elsevier Inc. All rights reserved.