Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes.
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.
Yea
Kyungmoo
K
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea.
Kim
Jaeyoon
J
Yoon
Jong Hyuk
JH
Kwon
Taewan
T
Kim
Jong Hyun
JH
Lee
Byoung Dae
BD
Lee
Hae-Jeong
HJ
Lee
Seung Jae
SJ
Kim
Jong-In
JI
Lee
Taehoon G
TG
Baek
Moon-Chang
MC
Park
Ho Seon
HS
Park
Kyong Soo
KS
Ohba
Motoi
M
Suh
Pann-Ghill
PG
Ryu
Sung Ho
SH
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D008244:Lysophosphatidylcholines; C495693:Slc2a4 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051745:Protein Kinase C-delta