Yea Kyungmoo, Kim Jaeyoon, Yoon Jong Hyuk, Kwon Taewan, Kim Jong Hyun, Lee Byoung Dae, Lee Hae-Jeong, Lee Seung Jae, Kim Jong-In, Lee Taehoon G, Baek Moon-Chang, Park Ho Seon, Park Kyong Soo, Ohba Motoi, Suh Pann-Ghill, Ryu Sung Ho
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea.
J Biol Chem. 2009 Dec 4;284(49):33833-40. doi: 10.1074/jbc.M109.024869. Epub 2009 Oct 8.
Glucose homeostasis is maintained by the orchestration of peripheral glucose utilization and hepatic glucose production, mainly by insulin. In this study, we found by utilizing a combined parallel chromatography mass profiling approach that lysophosphatidylcholine (LPC) regulates glucose levels. LPC was found to stimulate glucose uptake in 3T3-L1 adipocytes dose- and time-dependently, and this activity was found to be sensitive to variations in acyl chain lengths and to polar head group types in LPC. Treatment with LPC resulted in a significant increase in the level of GLUT4 at the plasma membranes of 3T3-L1 adipocytes. Moreover, LPC did not affect IRS-1 and AKT2 phosphorylations, and LPC-induced glucose uptake was not influenced by pretreatment with the PI 3-kinase inhibitor LY294002. However, glucose uptake stimulation by LPC was abrogated both by rottlerin (a protein kinase Cdelta inhibitor) and by the adenoviral expression of dominant negative protein kinase Cdelta. In line with its determined cellular functions, LPC was found to lower blood glucose levels in normal mice. Furthermore, LPC improved blood glucose levels in mouse models of type 1 and 2 diabetes. These results suggest that an understanding of the mode of action of LPC may provide a new perspective of glucose homeostasis.
葡萄糖稳态主要通过胰岛素对外周葡萄糖利用和肝脏葡萄糖生成的协调来维持。在本研究中，我们利用一种组合的平行色谱质谱分析方法发现溶血磷脂酰胆碱（LPC）可调节血糖水平。研究发现，LPC能剂量和时间依赖性地刺激3T3-L1脂肪细胞摄取葡萄糖，并且该活性对LPC中酰基链长度的变化以及极性头部基团类型敏感。用LPC处理导致3T3-L1脂肪细胞质膜上GLUT4水平显著增加。此外，LPC不影响IRS-1和AKT2的磷酸化，并且LPC诱导的葡萄糖摄取不受PI-3激酶抑制剂LY294002预处理的影响。然而，LPC对葡萄糖摄取的刺激作用被rottlerin（一种蛋白激酶Cδ抑制剂）和显性负性蛋白激酶Cδ的腺病毒表达所消除。与其确定的细胞功能一致，发现LPC可降低正常小鼠的血糖水平。此外，LPC改善了1型和2型糖尿病小鼠模型的血糖水平。这些结果表明，了解LPC的作用模式可能为葡萄糖稳态提供新的视角。
