Effect of YM-126414 on glucose uptake and redistribution of glucose transporter isotype 4 in muscle cells.
We discovered a novel compound, YM-126414 [1,3, 3-trimethyl-2-(2-phenylaminovinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeletal muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC(50)=10 nM). To investigate the mechanism of this stimulation, we determined the redistribution of insulin-regulatable glucose transporter isotype 4 (Glut4). When fully differentiated C2C12 cells stably expressing myc-tagged Glut4 protein were treated with YM-126414, redistribution was dramatically increased in a dose-dependent manner (EC(50)=21 nM). These results indicate that YM-126414 is a novel glucose uptake stimulator for muscle cells by causing up-regulation of Glut4 redistribution in differentiated muscle cells. Our findings for the in vitro effects of YM-126414 suggest a direction for the development of new drugs for the treatment of type 2 diabetes.
Shimokawa
T
T
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Ibaraki 305-8585, Tsukuba, Japan. simokawa@yamanouchi.co.jp
Kagami
M
M
Kato
M
M
Kurosaki
E
E
Shibasaki
M
M
Katoh
M
M
D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D007211:Indoles; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; C419845:YM 126414; D005947:Glucose