The mitochondrial outer membrane protein mitoNEET is a binding protein of the insulin sensitizer pioglitazone and is considered a novel target for the treatment of type II diabetes. In the present study, the authors assessed the pharmacologic properties of a novel small molecule, TT01001 [ethyl-4-(3-(3,5-dichlorophenyl)thioureido)piperidine-1-carboxylate]. TT01001 bound to mitoNEET without peroxisome proliferator-activated receptor γ activation effect. In db/db mice, TT01001 improved hyperglycemia, hyperlipidemia, and glucose intolerance, and its efficacy was equivalent to that of pioglitazone, without the pioglitazone-associated weight gain. Mitochondrial complex II + III activity of the skeletal muscle was increased in db/db mice and this elevated activity was suppressed by TT01001. This study is the first to demonstrate the effects of a mitoNEET ligand on glucose metabolism and mitochondrial function in an animal disease model. These findings support targeting mitoNEET as a potential therapeutic approach for the treatment of type II diabetes.
See article at J Pharmacol Exp Ther 2015, 352:338–345.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics