Circulating Endothelial Microparticles in Diabetes Mellitus

Background. Endothelial Microparticles (EMPs) are small vesicles shed from activated or apoptotic endothelial cells and involved in cellular cross-talk. Whether EMP immunophenotypes vary according to stimulus in Diabetes Mellitus (DM) is not known. We studied the cellular adhesion molecule (CAM) profile of circulating EMPs in patients with and without Diabetes Mellitus type 2, who were undergoing elective cardiac catheterization. Methods and Results. EMPs were analyzed by flow cytometry. The absolute median number of EMPs (EMPs/μL) specific for CD31, CD105, and CD106 was significantly increased in the DM population. The ratio of CD62E/CD31 EMP populations reflected an apoptotic process. Conclusion. Circulating CD31+, CD105+, and CD106+ EMPs were significantly elevated in patients with DM. EMPs were the only independent predictors of DM in our study cohort. In addition, the EMP immunophenotype reflected an apoptotic process. Circulating EMPs may provide new options for risk assessment

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD

Effects of body weight and alcohol consumption on insulin sensitivity

<p>Abstract</p> <p>Background</p> <p>Obesity is a risk factor for the development of insulin resistance, which can eventually lead to type-2 diabetes. Alcohol consumption is a protective factor against insulin resistance, and thus protects against the development of type-2 diabetes. The mechanism by which alcohol protects against the development of type-2 diabetes is not well known. To determine the mechanism by which alcohol improves insulin sensitivity, we fed water or alcohol to lean, control, and obese mice. The aim of this study was to determine whether alcohol consumption and body weights affect overlapping metabolic pathways and to identify specific target genes that are regulated in these pathways.</p> <p>Method</p> <p>Adipose tissue dysfunction has been associated with the development of type-2 diabetes. We assessed possible gene expression alterations in epididymal white adipose tissue (WAT). We obtained WAT from mice fed a calorie restricted (CR), low fat (LF Control) or high fat (HF) diets and either water or 20% ethanol in the drinking water. We screened the expression of genes related to the regulation of energy homeostasis and insulin regulation using a gene array composed of 384 genes.</p> <p>Results</p> <p>Obesity induced insulin resistance and calorie restriction and alcohol improved insulin sensitivity. The insulin resistance in obese mice was associated with the increased expression of inflammatory markers Cd68, Il-6 and Il-1α; in contrast, most of these genes were down-regulated in CR mice. Anti-inflammatory factors such as Il-10 and adrenergic beta receptor kinase 1 (Adrbk1) were decreased in obese mice and increased by CR and alcohol. Also, we report a direct correlation between body weight and the expression of the following genes: Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11), Lpin2 (lipin2), and Dusp9 (dual-specificity MAP kinase phosphatase 9).</p> <p>Conclusion</p> <p>We show that alcohol consumption increased insulin sensitivity. Additionally, alterations in insulin sensitivity related with obesity were coupled with alterations in inflammatory genes. We provide evidence that alcohol may improve insulin sensitivity by up-regulating anti-inflammatory genes. Moreover, we have indentified potential gene targets in energy metabolic pathways and signal transducers that may contribute to obesity-related insulin resistance as well as calorie restriction and alcohol-induced insulin sensitivity.</p

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis

Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases

The relationship of Physical performance and Osteoporosis prevention with vitamin D in older African Americans (PODA)

© 2017 Elsevier Inc. Rationale Vitamin D deficiency is associated with bone loss, poor muscle strength, falls and fracture. This information in older African Americans (AAs) is sparse. Objective The study of the relationship of Physical performance, Osteoporosis prevention with vitamin D in older African Americans (PODA) is a randomized, double-blind, placebo-controlled 3-year trial examining the effect of vitamin D on bone loss and physical performance in older AA women. Methods 260 healthy AA women aged \u3e 60 years were assigned to receive placebo or vitamin D3. Initial vitamin D3dose was determined by the baseline serum 25OHD level, and adjusted further to maintain serum 25OHD between 30 and 69 ng/ml. Subjects with baseline 25OHD levels ≤ 8 ng/ml or ≥ 26 ng/ml were excluded. Objective measures of neuromuscular strength [Short Physical Performance Battery (SPPB), grip strength and 6-minute walking distance (6MWD)] and bone mineral density (BMD) were obtained. Results SPPB gait speed, grip strength and 6MWD showed a significant positive correlation with free 25OHD. 1 pg/ml increase in free 25OHD predicted a 32% increase in the odds of having higher gait speed and a 1.42 lb. increase in grip strength. No significant differences in BMI, BMD, muscle mass, grip strength, serum total 25OHD and free 25OHD were observed between groups. None of the measures of physical performance showed an association with baseline serum 25OHD. Conclusions This is the first study to show an association between free 25OHD and physical performance. These findings indicate a positive relationship of free 25OHD with gait speed and grip strength in older AA women. Further studies are needed to understand the role of free 25OHD

Identity of the Escherichia coli cls and nov genes

cls and nov mutants have similar increased sensitivities to novobiocin and reduced levels of cardiolipin, both of which can be corrected by plasmid-borne copies of either wild-type gene. A comparison of the DNA sequences of both genes further verifies their identity