The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90±1.08 vs. 7.48±1.12 mmol/l, p=0.013). Consequently, adjusted ΔFPG was significantly higher in the AG+GG compared to the AA group (1.48±1.51 vs. 1.02±1.33 mmol/l, p=0.022). Similar trend was observed for HbA1c levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1., Z. Schroner ... [et al.]., and Obsahuje seznam literatury
Wnt/β-catenin signaling is involved in virtually every aspect of embryonic development and also controls homeostatic selfrenewal in a number of adult tissues. Recently, emerging evidence from researches of organ fibrosis suggest that sustained Wnt/β-catenin pathway reactivation is linked to the pathogenesis of fibrotic disorders. Here we focus on Wnt/β-catenin-related pathogenic effects in different organs, such as lung fibrosis, liver fibrosis, skin fibrosis and renal fibrosis. Additionally, Wnt/β- catenin signaling works in a combinatorial manner with TGF-β signaling in the process of fibrosis, and TGF-β signaling can induce expression of Wnt/β-catenin superfamily members and vice versa. Moreover, network analysis, based on pathway databases, revealed that key factors in the Wnt pathway were targeted by some differentially expressed microRNAs detected in fibrosis diseases. These findings demonstrated the crosstalks between Wnt/β-catenin pathway and TGF-β signalings, and microRNAs, highlighting the role of Wnts in organ fibrogenesis. Most importantly, nowadays there is a variety of Wnt pathway inhibitors which give us the potential therapeutic feasibility, modulation of the Wnt pathway may, therefore, present as a suitable and promising therapeutic strategy in the future., Y. Guo ... [et al.]., and Obsahuje seznam literatury