Project description:We identified that PBMC of individuals simultaneously affected by a combination of T2DM, dyslipidemia and periodontitis, showed altered molecular profile mainly associated to inflammatory response, immune cell trafficking, and infectious disease pathways Patients were divided into: T2DMpoorly-DL-P (n=5, Grupo 1), T2DMwell-DL-P (n=7, Grupo 2), DL-P (n=6, Grupo 3), P (n=6, Grupo 4) and Healthy (n=6, Control). T2DM poorly controlled = HbA1c ≥8.5%; T2DM well-controlled patients = HbA1c <7.0%
Project description:Insulin resistance and Type 2 Diabetes Mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. To identify the underlying molecular processes in preadipocytes of T2DM patients that are a characteristic of the development of T2DM, preadipocyte cell cultures were prepared from subcutaneous fat biopsies of T2DM patients and compared with age- and BMI matched control subjects. Gene expression profiling showed changed expression of transcription factors involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were down-regulated, and inflammation/apoptosis was up-regulated in T2DM preadipocytes. The down-regulation of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage. 7 T2DM preadipocyte samples and 9 age- and BMI-matched control samples were hybridized using 70-mer oligonucleotide microarrays. Samples were labeled with either Cy3 or Cy5. A total of 20 arrays were used including dye swop. Per array, a T2DM sample was hybridized with a control sample of the same gender and matched based on age and BMI. To ensure hybridization of two samples with the same gender, three T2DM (5064, 5128, 5395) and one control sample (5616) were used twice and listed as technical replicates.
Project description:Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Previous publication showed the obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. The goal of this experiment was to compare genome wide enrichment of H3K9ac histone mark profile of white blood cells of healthy controls, patients with obesity and/or stroke in order to understand the histone modifications differences behind the different phenotypes. There were 3 subjects in each group.
Project description:Insulin resistance and Type 2 Diabetes Mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. To identify the underlying molecular processes in preadipocytes of T2DM patients that are a characteristic of the development of T2DM, preadipocyte cell cultures were prepared from subcutaneous fat biopsies of T2DM patients and compared with age- and BMI matched control subjects. Gene expression profiling showed changed expression of transcription factors involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were down-regulated, and inflammation/apoptosis was up-regulated in T2DM preadipocytes. The down-regulation of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.
Project description:Objective: To explore the mechanism of Jiangtang Tiaozhi Recipe in the treatment of obese T2DM patients with dyslipidemia based on transcriptomics. Methods: We chose 6 patients with obese type 2 diabetes mellitus and dyslipidemia (syndrome of excess of gastrointestinal heat) who were treated by JTTZR for 24 weeks, while 6 cases included in the healthy control group. We selected 6 cases in each group (disease group before treatment, disease group after treatment and healthy control group) to start the research of lncRNA microarray. According to the differentially expressions of lncRNAs and mRNAs, we secondly performed GO analysis, Pathway analysis, and found out some target lncRNAs as well as their associated mRNAs. The trial register number is NCT04623567. Results: (1) Disease group before treatment vs. healthy control group: There are 557 upregulated lncRNAs, 273 downregulated lncRNAs, 491 upregulated mRNAs and 1639 downregulated mRNAs. (2) Disease group after treatment vs. Disease group before treatment: There are 128 upregulated lncRNAs, 32 downregulated lncRNAs, 45 upregulated mRNAs and 140 downregulated mRNAs.
Project description:Here, we performed a genome-wide promoter analysis of DNA methylation to screen for genes differentially methylated in T2DM.<br>We used methylated DNA immunoprecipitation (MeDIP), combined with microarray technology (Keshet et al., 2006; Weber et al., 2005), to discover whether changes in DNA methylation are specific to T2DM. A cohort of normal glucose tolerant (NGT) and Type 2 diabetic (T2DM) male volunteers was studied.
Project description:Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Previous publication showed the obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. The goal of this experiment was to compare the global transcriptional profile, and its regulation, of white blood cells of healthy normals, patients with obesity and/or stroke in order to understand the transcriptional differences behind the different phenotypes. There were 6 subjects in each group. RNA was purified from white blood cells using a TRIZOL RNA Isolation Protocol (Life technologies) and 500 ng of starting material were used as input for the Illumina TotalPrep Amplification Kit. Next, the Array Studio (OmicSoft Corporation) was used to generate a list of genes that are expressed at a significantly higher/lower level using the two-way ANOVA in order to analyze the 2x2 factorial design.
Project description:The ZDF rat, with spontaneous homozygous mutation of the leptin receptor gene (fa/fa), is one of the widely used animal model for studying the human type 2 diabetes mellitus (T2DM). Male ZDF rats have the symptoms of obesity and insulin resistance at a young age, accompanying with impaired islet function. However, their hepatic pathogenesis is still unclear. Based on the successive observations and the transcriptomic analyses of the liver tissue at 22 weeks old, we detected the typical clinical indications of T2DM, severe hepatic metabolic remodeling and the inflammatory liver injury in the ZDF rats. The integrin linked kinase signaling, as well as the endoplasmic reticulum stress and its downstream p38 MAPK signaling, seemed to play crucial roles in it. We have proved the ZDF rats could better simulate the pathogenesis of the human T2DM associated nonalcoholic fatty liver disease (NAFLD), and provided targets and reference for future T2DM studies.
Project description:Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However, a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects. Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased. Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration.