Microwave-assisted synthesis of chitooligosaccharide guanidine and its effect on GLUT4-dependent glucose uptake through an Akt-activated protein kinase signaling pathway in L6 skeletal muscle cells
Microwave-assisted synthesis of chitooligosaccharide guanidine and its effect on GLUT4-dependent glucose uptake through an Akt-activated protein kinase signaling pathway in L6 skeletal muscle cells
复制标题
微波辅助合成壳寡糖胍及其通过 L6 骨骼肌细胞中 Akt 激活蛋白激酶信号通路对 GLUT4 依赖性葡萄糖摄取的影响
DOI：
10.1039/c6ra17654b
复制
发表时间：
2016-09
期刊：
影响因子：
3.9
通讯作者：
Wu Yuntang
中科院分区：
文献类型：
--
作者：
Wang Li;Liu Zongbao;Liu Xiaofei;Wu Yuntang
参照二甲双胍的分子结构，采用微波辐射法合成了一种新的双胍类化合物壳寡糖胍（COSG）。既能降低二甲双胍对胃肠道系统的刺激作用，又能提高药物的生物活性。然后，进行细胞活力试验以检查壳寡糖（COS）和COSG的细胞毒性，并使用L6骨骼肌细胞建立胰岛素抵抗（IR）模型。观察COS和COSG对IR细胞活力和葡萄糖消耗的影响，并与二甲双胍和胰岛素进行比较。进一步研究GLUT4蛋白的表达、转位及Akt磷酸化水平，探讨其作用机制。结果表明，COS和COSG均无毒，与二甲双胍相比，COS和COSG能显著提高L6细胞的活力和葡萄糖摄取。此外，COSG促进葡萄糖摄取的效果更好，并呈剂量依赖性。COS可增加GLUT4蛋白的总表达量，但对GLUT4的膜转位无明显影响，而二甲双胍对GLUT4的总表达量和膜表达量均无明显影响。COSG对GLUT4蛋白的总表达量影响不大，但能显著提高GLUT4的膜表达量和Akt的磷酸化水平，这与胰岛素的作用一致。
With reference to the molecular structure of metformin, a new biguanide compound, namely, chitooligosaccharide guanidine (COSG), was synthesized by microwave irradiation. It could both reduce the stimulatory effect of metformin on the gastrointestinal system and increase the biological activity of the drugs. Then, a cell vitality test was conducted to examine the cell toxicity of chitooligosaccharide (COS) and COSG, and an insulin resistance (IR) model using L6 skeletal muscle cells was established. The influence of COS and COSG on the cell vitality and glucose consumption of IR cells was observed and compared with that of metformin and insulin. Moreover, the expression and translocation of GLUT4 protein and the phosphorylation level of Akt were further investigated to study the mechanism. The results showed that both COS and COSG were non-toxic and could improve the vitality and promote the uptake of glucose of L6 cells remarkably in comparison to metformin. Furthermore, the effect of COSG on promoting glucose uptake was better and dose-dependent. It was also found that COS could increase the total expression of GLUT4 protein but had no significant effect on the membrane translocation of GLUT4, whereas metformin exhibited little effect on either the total expression or the membrane expression of GLUT4. Moreover, COSG exerted little influence on the total expression of GLUT4 protein but led to significant improvement in the membrane expression of GLUT4 and phosphorylation level of Akt, which were consistent with the effect of insulin.
登录
查看更多内容
影响因子：
4.8
作者：
Nora M;Guimarães M;Almeida R;Martins P;Gonçalves G;Santos M;Morais T;Freitas C;Monteiro MP
通讯作者：
Monteiro MP
影响因子：
3.9
作者：
Ningning Xu;Derun Ding
通讯作者：
Ningning Xu;Derun Ding
影响因子：
3.2
作者：
Funakoshi H;Shiga T;Homma Y;Nakashima Y;Takahashi J;Kamura H;Ikusaka M
通讯作者：
Ikusaka M
影响因子：
3.9
作者：
H. Siqi;Zhiming Yu;Chusheng Qi;Zhang Yang
通讯作者：
H. Siqi;Zhiming Yu;Chusheng Qi;Zhang Yang
DOI：
10.1007/s00464-013-3147-5
发表时间：
2013
期刊：
Surgical Endoscopy
影响因子：
--
作者：
A. Cuschieri
通讯作者：
A. Cuschieri