title: Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes.
abstract: 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.
authors.affiliation: Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.forename: Taewan
authors.initials: T
authors.lastname: Kwon
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byoung Dae
authors.initials: BD
authors.lastname: Lee
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jong-In
authors.initials: JI
authors.lastname: Kim
authors.forename: Taehoon G
authors.initials: TG
authors.lastname: Lee
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Baek
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Motoi
authors.initials: M
authors.lastname: Ohba
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: 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
chemical_list: 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