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-phenylamino vinyl)-3H-indolium perchlorate], which stimulates glucose uptake in skeleta l muscle cells in vitro. This compound increased the rate of consumption of glucose by C2C12 mouse myoblast cells in a dose-dependent manner (EC50 = 1 0 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 increa sed in a dose-dependent manner (EC50 = 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 f indings for the in vitro effects of YM-126414 suggest a direction for the d evelopment of new drugs for the treatment of type 2 diabetes. (C) 2000 Else vier Science B.V. All rights reserved.