title: 3-O-Acyl-epicatechins Increase Glucose Uptake Activity and GLUT4 Translocation through Activation of PI3K Signaling in Skeletal Muscle Cells.
abstract: Tea catechins promote glucose uptake in skeletal muscle cells. In this study, we investigated whether the addition of an acyl group to the C-3 position of catechins to generate 3-O-acyl-catechins promoted glucose uptake in L6 myotubes. 3-O-Myristoyl-(-)-epicatechin (EC-C14) and 3-O-palmitoyl-(-)-epicatechin (EC-C16) promoted glucose uptake and translocation of glucose transporter (GLUT) 4 in the cells. The effect of 3-O-acyl-(-)-epicatechins was stronger than that of (-)-epicatechin (EC), whereas neither 3-O-myristoyl-(+)-catechin (C-C14) nor 3-O-palmitoyl-(+)catechin (C-C16) promoted glucose uptake or GLUT4 translocation as well as (+)-catechin (C). We further investigated an affinity of catechins and 3-O-acyl-catechins to the lipid bilayer membrane by using surface plasma resonance analysis. Maximum binding amounts of EC-C16 and C-C16 to the lipid bilayer clearly increased compared with that of (-)-EC and (+)-C, respectively. We also examined the mechanism of GLUT4 translocation and found EC-C14 and EC-C16 induced the phosphorylation of PI3K, but did not affect phosphorylation of Akt or IR. In conclusion, the addition of an acyl group to the C-3 position of (-)-EC increases its affinity for the lipid bilayer membrane and promotes GLUT4 translocation through PI3K-dependent pathways in L6 myotubes.
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan. mana5998bu@affrc.go.jp.|National Agriculture and Food Research Organization, National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan. mana5998bu@affrc.go.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ueda-Wakagi
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan. rmukai@tokushima-u.ac.jp.|Department of Food Science, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto, Tokushima 770-8503, Japan. rmukai@tokushima-u.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Mukai
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan. hb03e708@gmail.com.
authors.forename: Naoya
authors.initials: N
authors.lastname: Fuse
authors.affiliation: Laboratory of Food and Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan. mizushina@shinshu-u.ac.jp.|Graduate School of Agriculture, Shinshu University, Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan. mizushina@shinshu-u.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan. ashida@kobe-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
mesh_terms: D000818:Animals; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D008051:Lipid Bilayers; D002392:Catechin; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose
keywords: acyl catechin; glucose transporter 4; insulin signaling pathway; skeletal muscle