Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets.

摘要: Insulin resistance is the undisputed root cause of type 2 diabetes mellitus (T2DM). There currently an unmet demand for safe and effective insulin sensitizers, owing to restricted prescription or removal from market certain approved such as thiazolidinediones (TZDs), because safety concerns. Effective sensitizers without TZD-like side effects will therefore be invaluable diabetic patients. The specific focus on peroxisome proliferator-activated receptor γ- (PPARγ-) based agents in past decades may have impeded search novel safer sensitizers. This review discusses possible directions promising strategies future research development describes potential targets these agents. Direct PPARγ agonists, selective modulators (sPPARγMs), PPARγ-sparing compounds (including ligands mitochondrial target TZDs), that downstream effectors PPARγ, along with agents, heat shock protein (HSP) inducers, 5′-adenosine monophosphate-activated kinase (AMPK) activators, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, biguanides, chloroquines, which than traditional TZDs, been described. minireview thus aims provide fresh perspectives a new generation