Insulin stimulates expression of the pyruvate kinase m gene in 3T3-L1 adipocytes
Insulin stimulates expression of the pyruvate kinase m gene in 3T3-L1 adipocytes
复制标题
DOI：
10.1271/bbb.67.1272
复制
发表时间：
2003-06-01
影响因子：
1.6
通讯作者：
Noguchi, T
中科院分区：
文献类型：
--
作者：
Asai, Y;Yamada, K;Noguchi, T
M-2型丙酮酸激酶（M-2-PK）mRNA是脂肪细胞中PKM基因通过选择性RNA剪接产生的。我们发现胰岛素以时间和剂量依赖的方式增加3 T3-L1脂肪细胞中M2-PK mRNA的水平。这种诱导不需要培养基中存在葡萄糖或葡糖胺。胰岛素作用被胰岛素信号通路的药理学抑制剂阻断，如磷脂酰肌醇3-激酶（PI 3 K）抑制剂渥曼青霉素和丝裂原活化蛋白激酶（MAPK）激酶抑制剂PD 98059。一个稳定的报告基因表达试验表明，大鼠PKM基因的约2.2 kb的5 '侧翼区的启动子活性被胰岛素刺激，但这些刺激的程度低于mRNA的刺激。因此，我们认为，胰岛素通过涉及PI 3 K和MAPK激酶的信号通路，在转录和转录后水平上作用于脂肪细胞，从而增加M-2-PK mRNA的水平。
M-2-type pyruvate kinase (M-2-PK) mRNA is produced from the PKM gene by an alternative RNA splicing in adipocytes. We found that insulin increased the level of M2-PK mRNA in 3T3-L1 adipocytes in both time- and dose-dependent manners. This induction did not require the presence of glucose or glucosamine in the medium. The insulin effect was blocked by pharmacological inhibitors of insulin signaling pathways such as wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase. A stable reporter expression assay showed that the promoter activity of an about 2.2-kb 5'-flanking region of the rat PKM gene was stimulated by insulin, but the extents of these stimulations were lower than those of the mRNA stimulation. Thus, we suggest that insulin increases the level Of M-2-PK mRNA in adipocytes by acting at transcriptional and post-transcriptional levels through signaling pathways involving both PI3K and MAPK kinase.