Lysophosphatidylcholine Activates Adipocyte Glucose Uptake and Lowers Blood Glucose Levels in Murine Models of Diabetes
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- Lysophosphatidylcholine Activates Adipocyte Glucose Uptake and Lowers Blood Glucose Levels in Murine Models of Diabetes
- 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
- 3T3-L1 adipocytes; Acyl chain; Adipocytes; Blood glucose level; Cellular function; Dominant negative; Glucose homeostasis; Glucose level; Glucose production; Glucose uptake; In-line; Kinase inhibitors; LY294002; Lysophosphatidylcholine; Mode of action; Mouse models; Murine model; Plasma membranes; Polar headgroups; Pre-Treatment; Protein Kinase C
- Issue Date
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.284, no.49, pp.33833 - 33840
- 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 Cδ inhibitor) and by the adenoviral expression of dominant negative protein kinase Cδ. 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.
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