Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor involved in the regulation of lipid metabolism, diabetes, obesity, atherogenesis and inflammation.
This novel TZD has low affinity for binding and activation of PPARγ and has insulin-sensitizing effects in mouse models of diabetes and ability to lower glucose in Phase 2 clinical trials.
P-EGFR, PPARγ, AQP1 and NHE3 production in a rat model of diabetes (streptozotocin-induced hypertensive Ren-2 transgenic [mRen2]27 rats) and controls, with or without pioglitazone treatment, was determined by immunohistochemistry.
Biochemical, genetic and functional studies strongly indicate peroxisome proliferator-activated receptor-γ (PPARγ), a pleiotropic transcription factor, as a primary target in the treatment of diabetic retinopathy.In this issue, Song et al. detail the role of PPARγ in diabetic retinopathy-related disorders, illustrating PPARγ-mediated inhibition of diabetes-induced leukostasis and leakage, and its beneficial role in modulating inflammation, angiogenesis and apoptosis in retinal and endothelial cells.
None of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies or diabetes.
The C1431T polymorphism in peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to be associated with diabetes, obesity, and metabolic syndrome.
Accumulating evidences suggest that there are important cross-talks between Nrf2 and PPARγ, PGC1α, PI3K/Akt on regulating antioxidant enzymes and the development of diabetes.
Another PPARγ polymorphism, the C1431T, is in strong linkage disequilibrium with Pro12Ala and has been shown to be associated with body weight, but its association with diabetes is controversial.
The PPARγ-C161T CC homozygote genotype was associated with significantly increased CHD risk when compared with the T allele carriers (CT+TT) in CHD patients with diabetes (OR:1.951, 95%CI: 1.115-3.415, P = 0.019), whereas PPARγ-P12A polymorphism was not associated with CHD risk (P > 0.05).
The roles of Kruppel-like factor 6 and peroxisome proliferator-activated receptor-γ in the regulation of macrophage inflammatory protein-3α at early onset of diabetes.
Increased body mass index but not common vitamin D receptor, peroxisome proliferator-activated receptor γ, or cytokine polymorphisms confers predisposition to posttransplant diabetes.
Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes.
Long-term use of rosiglitazone, a synthetic PPARγ agonist and a drug to treat insulin resistance, increases fracture rates among patients with diabetes.
The authors highlight these challenges and biases using an illustrative example: meta-analysis of interactions between the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene and various diet and lifestyle factors in the risk of diabetes.