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PPAR Research
Volume 2017 (2017), Article ID 8360919, 13 pages
https://doi.org/10.1155/2017/8360919
Review Article

Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets

1Department of Pharmacy, The Second Hospital of Jilin University, Changchun 130041, China
2Department of Pharmacy, China-Japan Union Hospital of Jilin University, Changchun 130041, China
3Department of Pharmacy, Beijing Boai Hospital, China Rehabilitation Research Center, Beijing 100068, China
4Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Correspondence should be addressed to Xiujuan Fu; moc.361@300264jxf and Wei Chen; moc.621@54nehciew

Received 13 March 2017; Accepted 23 April 2017; Published 4 June 2017

Academic Editor: Brian N. Finck

Copyright © 2017 Yadan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.