title: Regulatory mechanism for the stimulatory action of genistein on glucose uptake in vitro and in vivo.
abstract: Genistein, an isoflavone, is known to possess diverse biological functions such as antioxidative and anti-inflammatory actions. It also acts like estrogen and inhibits several tyrosine kinases. Genistein was reported to suppress insulin-mediated glucose uptake in adipocytes. In this study, we investigated the effects of genistein on glucose uptake in vitro and in vivo as well as the mechanisms associated with the glucose uptake. We found that genistein decreased nonfasting blood glucose levels in KK-Ay/Ta Jcl mice, a type 2 diabetic animal model. It also dose-dependently induced insulin secretion by Rin-5F cells. In L6 myotubes, it directly stimulated glucose uptake independently of insulin under normal and high glucose conditions in dose-dependent manners. It promoted the translocation of glucose transporter 4 to the cell membrane under both glucose conditions. Based on studies using inhibitors of signaling molecules related to glucose uptake, the stimulatory effect of genistein on glucose uptake appeared to be dependent on the phosphatidylinositol 3-kinase, mammalian target of rapamycin, protein kinase C and 5'-adenosine-monophosphate-activated protein kinase pathway under both glucose conditions. In addition, O-GlcNAcylation by O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate, an inhibitor of N-acetylglucosaminidase, reduced the stimulatory effect of genistein on glucose uptake under both glucose conditions. Taken together, genistein may regulate glucose uptake by increasing the phosphorylation and decreasing the O-GlcNAcylation of proteins related to glucose homeostasis.
authors.affiliation: Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Byung Geun
authors.initials: BG
authors.lastname: Ha
authors.forename: Masato
authors.initials: M
authors.lastname: Nagaoka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Rima
authors.initials: R
authors.lastname: Tanabe
authors.forename: Je Tae
authors.initials: JT
authors.lastname: Woo
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kato
authors.forename: Ung-Il
authors.initials: UI
authors.lastname: Chung
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yagasaki
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019833:Genistein / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D051275:Glucose Transporter Type 4; D019833:Genistein; D005947:Glucose