Affiliation:
1. Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P. Box No. 114, Jazan, Saudi Arabia
Abstract
Peroxisome Proliferator-Activated Receptors (PPARs) also known as glitazone receptors are a family
of receptors that regulate the expression of genes and have an essential role in carbohydrate, lipid and protein
metabolism apart from other functions. PPARs come in 3 sub-types: PPAR-α, PPAR-β/δ and PPAR-γ - with
PPAR-γ having 2 isoforms - γ1 and γ2. Upon activation, the PPARs regulate the transcription of various genes
involved in lipid and glucose metabolism, adipocyte differentiation, increasing insulin sensitivity, prevention of
oxidative stress and to a certain extent, modulation of immune responses via macrophages that have been implicated
in the pathogenesis of insulin resistance. Hence, PPARs are an attractive molecular target for designing new
anti-diabetic drugs. This has led to a boost in the research efforts directed towards designing of PPAR ligands -
particularly ones that can selectively and specifically activate one or more of the PPAR subtypes. Though, PPAR-
γ full agonists such as Thiazolidinediones (TZDs) are well established agents for dyslipidemia and type 2 diabetes
mellitus (T2D), the side effect profile associated with TZDs has potentiated an imminent need to come up with
newer agents that act through this pathway. Several newer derivatives having TZD scaffold have been designed
using structure based drug designing technique and computational tools and tested for their PPAR binding affinity
and efficacy in combating T2D and some have shown promising activities. This review would focus on the role
of PPARs in the management of T2D; recently reported TZD derivatives which acted as agonists of PPAR- γ and
its subtypes and are potentially useful in the new drug discovery for the disease.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Reference135 articles.
1. Danaei G.; Finucane M.M.; Lu Y.; National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011,378(9785),31-40
2. Shin J.A.; Lee J.H.; Lim S.Y.; Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness. J Diabetes Investig 2013,4(4),334-343
3. Diabetes Atlas [homepage on internet]. International Diabetes
Federation (IDF) [cited 2019 Feb 10]. Available from: ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www.idf.org/diabetesatlas">http://www.idf.org/diabetesatlas
4. Chiarelli F.; Di Marzio D.; Peroxisome proliferator-activated receptor-γ agonists and diabetes: current evidence and future perspectives. Vasc Health Risk Manag 2008,4(2),297-304
5. Nesto R.W.; Bell D.; Bonow R.O.; Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004,27(1),256-263
Cited by
21 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献