Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase
Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase
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DOI：
10.1016/j.cellsig.2007.02.006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Bengtsson, Tore
中科院分区：
文献类型：
--
作者：
Hutchinson, Dana S.;Csikasz, Robert I.;Bengtsson, Tore
NADPH氧化酶抑制剂，如二苯基碘鎓（DPI）和夹竹桃素，降低全身和血糖水平，并改善糖尿病时，给予啮齿动物。骨骼肌在控制葡萄糖稳态中具有重要作用，我们使用L 6细胞、C2 C12细胞和原代肌细胞作为模型系统来研究这些药物是否调节骨骼肌细胞中的葡萄糖摄取。在这项研究中提出的数据表明，夹竹桃麻素不影响培养的骨骼肌细胞中的葡萄糖摄取。抑制NADPH氧化酶活性的嵌合肽达特gp 91 ds也不能影响葡萄糖摄取，并且我们在培养的骨骼肌细胞中没有发现NADPH氧化酶（检测的亚基是Nox 4、p22 phox、gp 91 phox和p47 phox mRNA）的显著证据。然而，DPI增加L 6细胞、C2 C12细胞和原代肌细胞中的基础和胰岛素刺激的葡萄糖摄取。对L 6细胞的详细研究表明，葡萄糖摄取的增加是通过一种不依赖于磷酸肌醇-3激酶（PI 3 K）/Akt而依赖于AMP激活的蛋白激酶（AMPK）的机制。我们推测DPI通过抑制线粒体复合物I和减少氧消耗，导致ATP减少和AMPK活化，刺激骨骼肌细胞的葡萄糖摄取。(c)2007年爱思唯尔公司All rights reserved.
NADPH oxidase inhibitors such as diphenylene iodonium (DPI) and apocynin lower whole body and blood glucose levels and improve diabetes when administered to rodents. Skeletal muscle has an important role in managing glucose homeostasis and we have used L6 cells, C2C12 cells and primary muscle cells as model systems to investigate whether these drugs regulate glucose uptake in skeletal muscle cells. The data presented in this study show that apocynin does not affect glucose uptake in skeletal muscle cells in culture. Tat gp91 ds, a chimeric peptide that inhibits NADPH oxidase activity, also failed to affect glucose uptake and we found no significant evidence of NADPH oxidase (subunits tested were Nox4, p22phox, gp91phox and p47phox mRNA) in skeletal muscle cells in culture. However, DPI increases basal and insulin-stimulated glucose uptake in L6 cells, C2C12 cells and primary muscle cells. Detailed studies on L6 cells demonstrate that the increase of glucose uptake is via a mechanism independent of phosphoinositide-3 kinase (PI3K)/Akt but dependent on AMP-activated protein kinase (AMPK). We postulate that DPI through inhibition of mitochondrial complex I and decreases in oxygen consumption, leading to decreases of ATP and activation of AMPK, stimulates glucose uptake in skeletal muscle cells. (c) 2007 Elsevier Inc. All rights reserved.