Lysophosphatidylcholine Activates Adipocyte Glucose Uptake and Lowers Blood Glucose Levels in Murine Models of Diabetes

作者：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^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284(49): 33833-33840.

DOI：10.1074/jbc.M109.024869

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 C delta inhibitor) and by the adenoviral expression of dominant negative protein kinase C delta. 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.

• 出版日期2009-12-4