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.
We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma(PPARgamma) with type 2 diabetes.
A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPARγ modulators (SPPARγMs) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPARγ full agonist drugs.
In view of inter-individual variability in therapeutic response to pioglitazone, this study was designed to search for an association between type 2 diabetes mellitus and Pro12Ala single-nucleotide polymorphism (SNP) in PPARγ (SNP rs1801282) and to investigate whether these genetic variants affect pioglitazone response in an Iranian population.
Together, these results showed that PPARGPro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.
Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D.
This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.
We measured the metabolic parameters and the expression of PPARgamma and PGC-1alpha mRNA using quantitative real-time PCR in omental and subcutaneous (SC) adipose tissues in an observational study of 153 individuals as well as in SC fat and skeletal muscle in an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and T2D) before and after intensive physical training for 4 weeks.
The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks.
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.
One region, upstream of the gene FAM78B, contains three binding sites for the transcription factor PPARG and two binding sites for HNF1A, both previously implicated in the pathology of type 2 diabetes.
Pro12Ala polymorphism of the PPARG2 gene is associated with type 2 diabetes mellitus and peripheral insulin sensitivity in a population with a high intake of oleic acid.
The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR-gamma) gene is inversely associated with body mass index (BMI), changes in BMI and the risk to develop type 2 diabetes mellitus.
Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.
Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population.
The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.
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.
The present study demonstrates that the AA genotype of the Gly482Ser polymorphism in the PPARGC1 gene might be a risk factor for diabetic retinopathy in the Slovene population (Caucasians) with type 2 diabetes (odds ratio 2.7, 95% confidence interval 1.0-6.8), whereas the Pro12Ala polymorphism of the PPARgamma gene failed to confer susceptibility to diabetic retinopathy.
Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D).
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.
Nominal interactions were observed for sleep duration and PPARGrs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).
Although the study was carried out on a sufficiently large sample, the conclusions do not support a major role for the Pro12Ala substitution of the PPAR-gamma gene in the etiology of type 2 diabetes.