Project description:Maternal diabetes is associated with a wide range of fetal and neonatal adverse effects including pulmonary disturbances. To investigate the effects of maternal diabetes on neonatal lung gene expression profile, we performed microarray analysis on the lungs of 14-day-old rats born to diabetic dam. Keywords: disease state analysis Four neonatal lungs exposed to maternal diabetes and four control lungs were analyzed.
Project description:Background and Aims: It is well demonstrated that in the beta cell population of the pancreas there is a dynamic turnover, which results from the net balance of several processes; beta cell replication, apoptosis and neogenesis. These processes have been studied in partial pancreatectomy and glucagon-like peptide 1 treated animals, where an increase in pancreas regeneration has been observed. Similarly, sodium tungstate, which decreases hyperglycemia in several animal models of diabetes, promotes a rise in the beta cell mass of nSTZ and STZ animals. However, the molecular mechanisms underlying this pancreas regeneration remain unknown. Therefore the objective of this study is to identify which genes are up or down regulated in the increase of the beta cell population of STZ rats treated with sodium tungstate. Materials and methods: Adult male Wistar (225-250 g) rats were kept under a constant 12-hour light-dark cycle and rats were kept under a constant 12-hour light-dark cycle and were allowed to eat and drink freely. Diabetes was induced by a single i.p. injection of streptozotocin (STZ) (70 mg/Kg body weight) in 0.9% NaCl with 100 mmol/L sodium citrate buffer (pH 4.5). Diabetes was confirmed by determination of its hyperglycaemia (>500mg/dL [Reflotron, Roche Diagnostic]). Healthy rats received an i.p. injection of the vehicle. Treatment started 7 days after the STZ or vehicle injection. Diabetic and healthy rats were divided into two groups. In the first (untreated), rats received deionized drinking water; in the second (treated) group, they were given a solution of sodium tungstate. During the first week of treatment, the rats received a solution of 0.7 mg/mL and in the next 4-5 weeks, the concentration was increased to 2 mg/mL. At the end of the experiment, the animals were sacrificed and pancreatic RNA isolated. Three chips (Affymetrix RAE-230A) were hybridized for each of the four experimental groups (untreated and treated healthy rats and untreated and treated diabetic rats). The raw intensity data obtained from the microarrays was normalized and summarized using the Bioconductor package RMA.
Project description:Increasing trends of obesity in childbearing women with a concurrent gestational diabetes are often associated with adverse fetal metabolic cues. Not only the carbohydrates but also fats are considered to contribute additional dietary fuels to the fetal hearts. To examine the hitherto unknown epigenetic mechanisms on the offspring’s cardiometabolic health due to maternal high-fat (HF) diet (40% kcal) or streptozotocin (STZ)-induced diabetic pregnancy, or both, we carried out an epigenetic characterization of neonatal heart tissue using chromatin immunoprecipitation (ChIP) sequening and a previously validated rat model. Chromatin landscape of offspring’s heart tissue revealed differential peaks distribution on various promoter regions mapped to the rat genome due to histone (H3) modifications by acetylation (H3Ac) or trimethylations of lysine 4 and 27 (H3K4me3 and H3K27me3, respectively). Ongoing evaluations include gene ontology and disease ontology analyses. Together, it is expected that the findings will show that maternal HF-diet with or without gestational diabetes changes the cardiac histone signature in rat offspring, potentially leading to development of novel disease prevention strategies.
