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Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets

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), b...

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Autores principales: Chen, Yadan, Ma, Haiming, Zhu, Dasheng, Zhao, Guowei, Wang, Lili, Fu, Xiujuan, Chen, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474250/
https://www.ncbi.nlm.nih.gov/pubmed/28659972
http://dx.doi.org/10.1155/2017/8360919
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author Chen, Yadan
Ma, Haiming
Zhu, Dasheng
Zhao, Guowei
Wang, Lili
Fu, Xiujuan
Chen, Wei
author_facet Chen, Yadan
Ma, Haiming
Zhu, Dasheng
Zhao, Guowei
Wang, Lili
Fu, Xiujuan
Chen, Wei
author_sort Chen, Yadan
collection PubMed
description 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.
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spelling pubmed-54742502017-06-28 Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets Chen, Yadan Ma, Haiming Zhu, Dasheng Zhao, Guowei Wang, Lili Fu, Xiujuan Chen, Wei PPAR Res Review Article 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. Hindawi 2017 2017-06-04 /pmc/articles/PMC5474250/ /pubmed/28659972 http://dx.doi.org/10.1155/2017/8360919 Text en Copyright © 2017 Yadan Chen et al. https://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Review Article
Chen, Yadan
Ma, Haiming
Zhu, Dasheng
Zhao, Guowei
Wang, Lili
Fu, Xiujuan
Chen, Wei
Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title_full Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title_fullStr Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title_full_unstemmed Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title_short Discovery of Novel Insulin Sensitizers: Promising Approaches and Targets
title_sort discovery of novel insulin sensitizers: promising approaches and targets
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474250/
https://www.ncbi.nlm.nih.gov/pubmed/28659972
http://dx.doi.org/10.1155/2017/8360919
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