Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through [alpha]2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of [alpha]2A-AR in bone. The aim of this study was to investigate the presence of [alpha]2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate [alpha]2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in [alpha]2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-timePCR, genetic association study between rs553668 A)G and rs1800544 C)GSNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. [alpha2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on [alpha]2A-AR mRNA level in human bone samples through the stability of mRNA. [alpha]2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that [alpha]2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in [alpha]2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis.
COBISS.SI-ID: 3887217
A 12-week prospective randomized open-label study was conducted with 45 obese women with PCOS diagnosed by the ASRM-ESHRE Rotterdam criteria. They were randomized to metformin (MET) 1000 mg BID or liraglutide (LIRA) 1.2 mg QD s.c. or roflumilast (ROF) 500 mcg QD. The primary outcome was change in measures of obesity. Short-term monotherapy with liraglutide or roflumilast was associated with significant weight loss in obese PCOS. Liraglutide was superior to metformin, whereas roflumilast resulted in greater, yet not statistically significant, mean weight loss when compared to metformin. Reduction of body weight with liraglutide resulted in improvement of body composition.
COBISS.SI-ID: 2323372
Background. It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D. Methods. In total 181 clinically well-characterised T2D patients were genotyped for NLRP3 rs35829419 and CARD8 rs2043211. Risk for diabetic complications was assessed using logistic regression. Results. Patients with median duration of T2D 11 (6-17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications (P=0.007 and P0.031 ). NLRP3 rs35829419 was associated with increased risk for macrovascular complications (P=0.004), with myocardial infarction in particular (P=0.052). No association was observed between CARD8 polymorphism and any of T2D complications. Conclusions. Our preliminary data suggest the role of NLRP3 polymorphism in diabetic macrovascular complications, especially in myocardial infarction.
COBISS.SI-ID: 32035801