Rosiglitazone (RG) is a well-known activator of peroxisome proliferator-activated receptor-gamma (PPAR<i>γ</i>) and used to treat hyperglycemia and type 2 diabetes; however, its clinical application has been confounded by adverse side effects.
Accumulating evidence suggests that inhibition of mitogen-activated protein kinase signalling can reduce phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) at serine 273, which mitigates obesity-associated insulin resistance and might be a promising treatment for type 2 diabetes.
In addition to improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best-characterized target PPARγ have been proposed as a therapeutic option for cancer treatment.
An interaction between ERRα and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) has also recently been shown to regulate an enzyme in the β-oxidation of free fatty acids, thereby suggesting that ERRα plays an important role in obesity and type 2 diabetes.
HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca<sup>2+</sup>]<sub>i</sub>, whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1<sup>-/-</sup> Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM.
Indeed, altered PPARγ transcriptional activity contributes to metabolic syndromes (obesity and hyperglycemia associated with type 2 diabetes mellitus), stroke and neurodegenerative diseases.
Role of peroxisome proliferator-activated receptor-gamma activation on visfatin, advanced glycation end products, and renal oxidative stress in obesity-induced type 2 diabetes mellitus.
RSV was used to treat rats with STZ-induced T2DM and the results indicated that RSV reversed the STZ-induced downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, SIRT1 and forkhead box protein O 3a.
The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and is the target for the insulin-sensitizing thiazolidinedione (TZD) drugs used to treat type 2 diabetes.
In humans, PPAR<sub>α</sub> activation causes a decrease in plasma triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL) lipolysis, whereas PPARγ agonists act as insulin sensitizers and improve insulin resistance, which is very useful in patients with type 2 diabetes mellitus (T2DM).
However, the potential for environmental PPARγ ligands to induce adverse metabolic effects has been questioned because PPARγ is a therapeutic target in treatment of type II diabetes.
In the in vivo experiments spontaneously hypertensive rats (SHRs) with induced T2D were treated with PSM or pioglitazone as a referent PPARγ full agonist, and pathology-relevant biochemical markers were analysed.
Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only).
By combining the lowering serum triglyceride levels benefit of PPARα agonists (such as fibrates) with the glycemic advantages of the PPARγ agonists (such as TZD), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence, has become a promising strategy for designing effective drugs against type-2 diabetes.
Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose.Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries such as stroke by mitigating the influence of comorbidities.
Potential role of peroxisome proliferator activated receptor gamma activation on serum visfatin and trace elements in high fat diet induced type 2 diabetes mellitus.
Thiazolidinedione, a PPARγ agonistic drug for type 2 diabetes mellitus, is widely used clinically but can induce adverse effects such as hepatotoxicity and SKM injury, as has been reported in recent decades.
These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.
Thus, comp#91 could be identified as a promising lead in the development of dual AT<sub>1</sub>R antagonist and PPARγ partial agonist against hypertension and type 2 diabetes.
A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications.