Kayali Ayse G, Austin Darrell A, Webster Nicholas J G
Medical Research Service, San Diego Veterans Affairs Healthcare System, California 92161, USA.
Endocrinology. 2002 Oct;143(10):3884-96. doi: 10.1210/en.2002-220259.
There is increasing evidence that protein kinase C (PKC) isoforms modulate insulin-signaling pathways in both positive and negative ways. Recent reports have indicated that the novel PKCdelta mediates some of insulin's actions in muscle and liver cells. Many studies use the specific inhibitor rottlerin to demonstrate the involvement of PKCdelta. In this study, we investigated whether PKCdelta might play a role in 3T3-L1 adipocytes. We found that PKCdelta is highly expressed in mouse adipose tissue and increased on 3T3-L1 adipocyte differentiation, and insulin-stimulated glucose transport is blocked by rottlerin. The phosphorylation state and activity of PKCdelta are not altered by insulin, but the protein translocates to membranes following insulin treatment. In contrast to the results with rottlerin, inhibition of PKCdelta activity or expression has no effect on glucose transport in adipocytes, unlike muscle cells. Lastly, we found that rottlerin lowers adenosine triphosphate levels in 3T3-L1 cells by acting as a mitochondrial uncoupler, and this is responsible for the observed inhibition of glucose transport.
越来越多的证据表明，蛋白激酶C（PKC）亚型以正向和负向方式调节胰岛素信号通路。最近的报告表明，新型PKCδ介导胰岛素在肌肉和肝细胞中的一些作用。许多研究使用特异性抑制剂rottlerin来证明PKCδ的参与。在本研究中，我们调查了PKCδ是否可能在3T3-L1脂肪细胞中发挥作用。我们发现PKCδ在小鼠脂肪组织中高度表达，并且在3T3-L1脂肪细胞分化时增加，并且rottlerin可阻断胰岛素刺激的葡萄糖转运。胰岛素不会改变PKCδ的磷酸化状态和活性，但胰岛素处理后该蛋白会转位至细胞膜。与rottlerin的结果相反，抑制PKCδ活性或表达对脂肪细胞中的葡萄糖转运没有影响，这与肌肉细胞不同。最后，我们发现rottlerin通过作为线粒体解偶联剂降低3T3-L1细胞中的三磷酸腺苷水平，这是观察到的葡萄糖转运抑制的原因。
