Stimulation of glucose uptake by theasinensins through the AMP-activated protein kinase pathway in rat skeletal muscle cells.
Theasinensins, dimeric catechins, have been reported to possess anti-hyperglycemic activity, but the underlying mechanism for this activity remains unknown. In this study, the effect of theasinensins A and B on glucose uptake into rat skeletal muscle cells (L6 myotubes) was investigated. A glucose uptake study using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) indicated that both theasinensins A and B stimulated glucose uptake in a concentration-dependent manner and translocation of glucose transporter 4 (GLUT4) to the plasma membrane. In addition, inhibition studies measuring 2-NBDG uptake in L6 cells revealed that compound C (AMP-activated protein kinase inhibitor) suppressed theasinensin-stimulated glucose uptake, whereas genistein (insulin receptor tyrosine kinase inhibitor) and wortmannin (phosphatidylinositol 3-kinase inhibitor) were inactive. Subsequent experiments on GLUT4-related signaling pathways in L6 cells demonstrated that theasinensins promoted the phosphorylation of AMPK, but not that of Akt, and that the theasinensin-promoted glucose uptake was blocked in the presence of a CaMKK inhibitor. The promotion of AMPK phosphorylation by theasinensins was not blocked in LKB1-knockdown cells. Consequently, it was concluded that theasinensins A and B did in fact promote GLUT4 translocation to the plasma membrane in L6 myotubes through the CaMKK/AMPK signaling pathway, but not through the PI3K/Akt pathway.
Department of Bioscience and Biotechnology, Division of Bioresource and Bioenviromental Sciences, Faculty of Agriculture, Graduated School of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan.
Ju
J
Qiu
Department of Bioscience and Biotechnology, Division of Bioresource and Bioenviromental Sciences, Faculty of Agriculture, Graduated School of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan.
Kanako
K
Maekawa
Department of Bioscience and Biotechnology, Division of Bioresource and Bioenviromental Sciences, Faculty of Agriculture, Graduated School of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan.
Yuko
Y
Kitamura
Department of Nutrition, University of Nagasaki, 1-1-1 Manabino, Nagayo-cho, Nishisonogi-gun, Nagasaki 851-2195, Japan.
Yuji
Y
Miyata
Department of Nutrition, University of Nagasaki, 1-1-1 Manabino, Nagayo-cho, Nishisonogi-gun, Nagasaki 851-2195, Japan.
Kazunari
K
Tanaka
Graduate School of Biochemical Science, Nagasaki University, 1-14 Bukyo-machi, Nagasaki 852-8521 Japan.
Takashi
T
Tanaka
College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501 Japan.
Minoru
M
Soga
College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501 Japan.
Takanori
T
Tsuda
Department of Bioscience and Biotechnology, Division of Bioresource and Bioenviromental Sciences, Faculty of Agriculture, Graduated School of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581, Japan. Electronic address: tmatsui@agr.kyushu-u.ac.jp.
Toshiro
T
Matsui
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D001578:Benzopyrans; D051275:Glucose Transporter Type 4; D010636:Phenols; C495694:Slc2a4 protein, rat; C576796:epigallocatechin-3-O-gallate epigallocatechin dimer; C481298:theasinensin A; D002392:Catechin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
AMPK; CaMKK; Glucose uptake; L6 cells; Theasinensin