scholarly journals Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs

2017 ◽  
Vol 2017 ◽  
pp. 1-20 ◽  
Author(s):  
Neelaveni Thangavel ◽  
Mohammed Al Bratty ◽  
Sadique Akhtar Javed ◽  
Waquar Ahsan ◽  
Hassan A. Alhazmi
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Potential ◽  
Antidiabetic Drugs ◽  
New Drugs ◽  
Antidiabetic Activity ◽  
Future Research ◽  
Structural Domain ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.

scholarly journals Pioglitazone in the Treatment of Type 2 Diabetes: Safety and Efficacy Review

2010 ◽  
Vol 3 ◽  
pp. CMED.S5372 ◽  
Author(s):  
Cyrus V. Desouza ◽  
Vijay Shivaswamy
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Ppar Gamma ◽  
New Drugs ◽  
Peroxisome Proliferator ◽  
Cardiovascular Safety ◽  
Peroxisome Proliferator Activated Receptor ◽  
Safety And Efficacy ◽  
Beneficial Effects

The increase in obesity and the aging of the population has lead to an increase in the incidence of type 2 diabetes. This has led to the development of new drugs such as thiazolidinediones (TZDs) which are Peroxisome Proliferator-Activated Receptor (PPAR-gamma) agonists, to treat type 2 diabetes. TZDs have recently been at the center of a controversy with regards to their cardiovascular safety. Pioglitazone is a TZD which has been shown to be effective in glycemic control by lowering insulin resistance. Pioglitazone also has beneficial effects on lipid metabolism and cardiovascular risk. The safety and efficacy of pioglitazone including its pleotropic effects are discussed at length in this article.

Role of PPARγ in renoprotection in Type 2 diabetes: molecular mechanisms and therapeutic potential

2008 ◽  
Vol 116 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Jichun Yang ◽  
Dongjuan Zhang ◽  
Jing Li ◽  
Xiaoyan Zhang ◽  
Fenling Fan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Large Body ◽  
Underlying Mechanism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Underlying Mechanisms ◽  
Stage Renal Disease

DN (diabetic nephropathy) is a chronic disease characterized by proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis with loss of renal function. DN is the leading cause of ESRD (end-stage renal disease), accounting for millions of deaths worldwide. TZDs (thiazolidinediones) are synthetic ligands of PPARγ (peroxisome-proliferator-activated receptor γ), which is involved in many important physiological processes, including adipose differentiation, lipid and glucose metabolism, energy homoeostasis, cell proliferation, inflammation, reproduction and renoprotection. A large body of research over the past decade has revealed that, in addition to their insulin-sensitizing effects, TZDs play an important role in delaying and preventing the progression of chronic kidney disease in Type 2 diabetes. Although PPARγ activation by TZDs is in general considered beneficial for the amelioration of diabetic renal complications in Type 2 diabetes, the underlying mechanism(s) remains only partially characterized. In this review, we summarize and discuss recent findings regarding the renoprotective effects of PPARγ in Type 2 diabetes and the potential underlying mechanisms.

Bezafibrate, a peroxisome proliferator–activated receptor α agonist, decreases circulating CD14+CD16+ monocytes in patients with type 2 diabetes

2015 ◽  
Vol 165 (2) ◽  
pp. 336-345 ◽  
Author(s):  
Tomoko Terasawa ◽  
Yoshimasa Aso ◽  
Kyoko Omori ◽  
Maiko Fukushima ◽  
Atsushi Momobayashi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Peroxisome Proliferator-Activated Receptor γ and Adipose Tissue—Understanding Obesity-Related Changes in Regulation of Lipid and Glucose Metabolism

2006 ◽  
Vol 92 (2) ◽  
pp. 386-395 ◽  
Author(s):  
Arya M. Sharma ◽  
Bart Staels
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Endocrine Function ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Abstract Context: Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation). Evidence Acquisition: Articles on the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990–2006). Evidence Synthesis: Articles were assessed to provide a comprehensive overview of how PPARγ-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis. Conclusions: PPARγ is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and adipocyte phenotype and up-regulates genes involved in fatty acid metabolism and triglyceride storage. Furthermore, PPARγ activation is associated with potentially beneficial effects on the expression and secretion of a range of factors, including adiponectin, resistin, IL-6, TNFα, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and angiotensinogen, as well as a reduction in plasma nonesterified fatty acid supply. The effects of PPARγ also extend to macrophages, where they suppress production of inflammatory mediators. As such, PPARγ activation appears to have a beneficial effect on the relationship between the macrophage and adipocyte that is distorted in obesity. Thus, PPARγ-activating ligands improve adipose tissue function and may have a role in preventing progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.

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