Send to

Choose Destination
PPAR Res. 2017;2017:8360919. doi: 10.1155/2017/8360919. Epub 2017 Jun 4.

Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets.

Author information

Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China.
Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun 130041, China.
Department of Pharmacy, Beijing Boai Hospital, China Rehabilitation Research Center, Beijing 100068, China.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.


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

Supplemental Content

Full text links

Icon for Hindawi Limited Icon for PubMed Central
Loading ...
Support Center