Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice.
Daidzein shows estrogenic, antioxidant and antiandrogenic properties as well as cell cycle regulatory activity. However, the antihyperglycemic effect of daidzein remains to be elucidated. In this study, we investigated the in vitro effect of daidzein on glucose uptake, AMPK phosphorylation and GLUT4 translocation on plasma membrane in L6 myotubes and its in vivo antihyperglycmic effect in obese-diabetic model db/db mice. Daidzein was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence. Promotion by daidzein of glucose uptake as well as GLUT4 translocation to plasma membrane by immunocytochemistry was also demonstrated in L6 myoblasts transfected with a GLUT4 cDNA-coding vector. Daidzein (0.1% in the diet) suppressed the rises in the fasting blood glucose, serum total cholesterol levels and homeostasis model assessment index of db/db mice. In addition, daidzein supplementation markedly improved the AMPK phosphorylation in gastrocnemius muscle of db/db mice. Daidzein also suppressed increases in blood glucose levels and urinary glucose excretion in KK-Ay mice, another Type 2 diabetic animal model. These in vitro and in vivo findings suggest that daidzein is preventive for Type 2 diabetes and an antidiabetic phytochemical.
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan; Department of Biotechnology, Konkuk University, Chungju 380-701, Republic of Korea.
Sun Hee
SH
Cheong
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Keisuke
K
Furuhashi
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Katsuki
K
Ito
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Masato
M
Nagaoka
Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo 113-8654, Japan.
Takayuki
T
Yonezawa
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Yutaka
Y
Miura
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan; Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo 113-8654, Japan. Electronic address: yagasaki@cc.tuat.ac.jp.
Kazumi
K
Yagasaki
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D007529:Isoflavones; C495693:Slc2a4 protein, mouse; C004742:daidzein; D000263:Adenylate Kinase; D005947:Glucose
AMP-activated protein kinase; AMPK; Daidzein; GLUT4; Glucose transporter 4; Glucose uptake; L6 myocytes; glucose transporter 4.