Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung City 40401, Taiwan, ROC.
Neurosci Lett. 2009 Nov 13;465(2):177-80. doi: 10.1016/j.neulet.2009.08.026. Epub 2009 Aug 12.
The present study is designed to investigate the role of atypical protein kinase C (PKC) in the signaling of mu-opioid receptors (MOR) for glucose uptake in myoblast C(2)C(12) cells. Loperamide enhanced the uptake of radioactive deoxyglucose into C(2)C(12) cells in a concentration-dependent manner that was abolished in cells pre-incubated with GF109203X at concentrations sufficient to block PKC. Inhibition of the atypical zeta (zeta) isoform of PKC using myristoylated PKC pseudosubstrate resulted in a concentration-dependent decrease of loperamide-stimulated glucose uptake into C(2)C(12) cells. In addition, loperamide elicited the phosphorylation of PKC-zeta in C(2)C(12) cells in a concentration-dependent manner that was abolished by pretreatment with naloxonazine at concentrations sufficient to block MOR. These results suggest the mediation of PKC-zeta in MOR signaling for glucose uptake in C(2)C(12) cells. Activation of PKC-zeta by MOR stimulation is highly relevant to the search for therapeutic targets for glucose transport in insulin-sensitive tissues.
本研究旨在探讨非典型蛋白激酶 C（PKC）在肌母细胞 C(2)C(12)细胞中 μ 阿片受体（MOR）信号转导促进葡萄糖摄取中的作用。洛哌丁胺以浓度依赖的方式增强放射性脱氧葡萄糖向 C(2)C(12)细胞的摄取，而在预先用足以阻断 PKC 的 GF109203X 孵育的细胞中，这种作用被消除。使用豆蔻酰化 PKC 假底物抑制非典型 ζ（zeta）同工型 PKC，导致洛哌丁胺刺激的 C(2)C(12)细胞葡萄糖摄取呈浓度依赖性下降。此外，洛哌丁胺以浓度依赖的方式诱导 C(2)C(12)细胞中 PKC-zeta 的磷酸化，而预先用足以阻断 MOR 的纳洛酮嗪处理则消除了这种作用。这些结果表明，PKC-zeta 在 C(2)C(12)细胞中 MOR 信号转导促进葡萄糖摄取中起介导作用。MOR 刺激激活 PKC-zeta 与寻找胰岛素敏感组织中葡萄糖转运的治疗靶点密切相关。
