1-Deoxynojirimycin Isolated from a Bacillus subtilis Stimulates Adiponectin and GLUT4 Expressions in 3T3-L1 Adipocytes
1-Deoxynojirimycin Isolated from a Bacillus subtilis Stimulates Adiponectin and GLUT4 Expressions in 3T3-L1 Adipocytes
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DOI：
10.4014/jmb.1209.09043
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发表时间：
2013-05-01
影响因子：
2.8
通讯作者：
Chung, Ji Hyung
中科院分区：
文献类型：
--
作者：
Lee, Seung-Min;Do, Hyun Ju;Chung, Ji Hyung
我们已经证明从枯草芽孢杆菌中分离的1-脱氧野生霉素(DNJ)可以提高分化的3T3-L1脂肪细胞的脂联素及其受体的水平，这被证明是有效的降血糖和增强胰岛素敏感性。在脂联素及其受体(AdipoR1和AdipoR2)的表达水平方面，低至0.5mU M的DNJ对分化的3T3-L1脂肪细胞均无毒性作用，并可提高AdipoR1和AdipoR2的转录水平。此外，DNJ还显著增加了5‘-腺苷一磷酸活化蛋白激酶(AMPK)的磷酸化水平。最后，DNJ处理导致葡萄糖转运蛋白4(GLUT4)的mRNA表达增加，根据2-脱氧-D-[H-3]葡萄糖摄取实验结果，脂肪细胞对葡萄糖的摄取显著增加。我们的发现表明，DNJ可能通过上调脂联素及其受体基因的表达来增加脂联素的作用，从而极大地促进脂肪组织对葡萄糖的摄取。此外，DNJ的降糖作用可能是通过GLUT4基因转录水平的增加和AMPK的激活增加质膜中GLUT4蛋白的丰度来实现的。
We have demonstrated that 1-deoxynojirimycin (DNJ) isolated from Bacillus subtilis MORE could enhance the levels of adiponectin and its receptors in differentiated 3T3-L1 adipocytes, which has been shown to be effective in lowering blood glucose levels and enhancing insulin sensitivity. DNJ was not toxic to differentiated 3T3-L1 adipocytes for up to a concentration of 5 M. In terms of expression levels of adiponectin and its receptors (AdipoR1 and AdipoR2), DNJ in concentrations as low as 0.5 mu M elevated both mRNA and protein levels of adiponectin and transcript levels of AdipoR1 and AdipoR2. In addition, DNJ increased phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) in a statistically significant manner. Finally, treatment with DNJ resulted in increased mRNA expression of glucose transporter 4 (GLUT4), which encodes for a glucose transporter, along with a significant increase in glucose uptake into the adipocytes based on results of a 2-deoxy-D-[H-3] glucose uptake assay. Our findings indicate that DNJ may greatly facilitate glucose uptake into adipose tissues by increasing the action of adiponectin via its up-regulated expression as well as its receptor genes. In addition, the glucose-lowering effects of DNJ may be achieved by an increased abundance of GLUT4 protein in the plasma membrane, as a consequence of the increased transcript levels of the GLUT4 gene and the activation of AMPK.