Single-cell transcriptomics implicate the alteration of peripheral immune cells and interaction with renal macrophages driven by T2DM
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216886 | GEO | 2023/12/01
REPOSITORIES: GEO
Similar Datasets
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.
2010-11-29 | GSE19420 | GEO
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.
2010-05-16 | E-GEOD-15790 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (T2DM) causes gastroparesis, delayed intestinal transit, and constipation, for unknown reasons. Complications are predominant in men and postmenopausal women, suggesting a female hormone-mediated mechanism. Low G-protein coupled estrogen receptor (GPER) expression from epigenetic modifications may explain it. We explored sexually differentiated GPER expression and gastrointestinal symptoms related to GPER alterations in wild-type (WT) and T2DM mice (db/db). GPER mRNA and protein expression, DNA methylation and histone modifications were measured from stomach and colon samples of db/db and WT mice. We found that WT female tissues have the highest GPER mRNA and protein expressions. The expression is lowest in all db/db. The lowest mRNA levels are in the male stomach and female colon. GPER downregulation is associated with promoter hypermethylation and reduced enrichment of H3K4me3 and H3K27ac marks around the GPER promoter. T2DM impairs gut GPER expression, and epigenetic sex-specific mechanisms matter in the downregulation.
2023-12-15 | GSE240515 | GEO
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.
2009-12-31 | GSE15790 | GEO
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.
2010-07-15 | E-MEXP-2253 | biostudies-arrayexpress
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.
2019-05-01 | GSE117447 | GEO
Project description:Eight-week-old C57BL/6J and T2DM db/db mice randomly divided into 4 groups of 8 based on equal bodyweight and fasting blood glucose (FBG) levels (mice were fasted for 6 h). The C57BL/6J mice (normal group) were treated with saline. The T2DM db/db mice were treated with saline, DLE (200 mg/kg), WTE (180 mg/kg), or pioglitazone (PGZ, 20 mg/kg) for 12 weeks, and were called the model group, DLE group, WTE group and PGZ group, respectively. All mice received oral administration of the indicated treatments once a day. After 12 weeks drug administration, liver aliquots from four randomly selected mice from the normal, model, PGZ and DLE groups were ground into powder in liquid nitrogen, followed by RNAseq for differentially expressed gene determination and pathway enrichment analysis.
2021-04-01 | GSE171269 | GEO
Project description:To search long noncoding RNAs (lncRNAs) which regulating energy metabolism in high fat diet induced T2DM mouse, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in epididymal adipose tissue in normal and high fat diet induced mouse. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators in epididymal adipose tissue under high fat diet induced T2DM mouse.
2019-06-01 | GSE100028 | GEO
Project description:T2DM patients with obesity and healthy volunteer Metagenome
| PRJNA560728 | ENA
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%
2020-08-28 | GSE156993 | GEO