CircRNA-mediated ceRNA regulatory networks: transcriptomic insights into obesity type 2 diabetes progression and treatment strategies.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE278204 | GEO | 2025/02/19
REPOSITORIES: GEO
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Project description:Aim: To study the effect of electroacupuncture (EA) on circRNA expression of plasma Exosomes and signal pathway of type 2 diabetic mice (T2DM). Methods: 10 mice were randomly selected as normal group. 20 mice were for T2DM model preparation and then were randomly divided into model and model + EA group. Mice in model + EA group were given EA treatment. The changes of fasting blood glucose (FBG) and the Islet structure were evaluated. Plasma exosomes of mice were subjected to RNA sequencing. Bioinformatics analysis on differentially expressed circRNA was performed. 12 differentially expressed circRNA were confirmed for real-time quantitative PCR (qPCR). Results: EA treatment reduced the FBG, preserved islets structure and reduced the islet β cell apoptotic rate of T2DM mice. RNA-sequencing analysis showed EA treatment lead to significant change of 165 circRNA expressions. GO and KEGG revealed that the effects of EA on T2DM mainly focus on regulating the functions and pathways related to multi-link metabolism, cell growth and organ development. Especially, the thyroid hormone signaling pathway was actively regulated by EA. circRNA/miRNA interactions analysis revealed that that mmu-mir-7092-3p was closely combined with circINPP4B, suggesting phosphatidylinositol signaling pathway was affected by EA. 12 circRNAs were identified to have significant differences by qRT-PCR. Conclusion: EA intervention can significantly protect islet function and improve FBG in T2DM, which may be related to the regulation on thyroid hormone and Phosphatidylinositol signaling pathway.
2019-07-02 | GSE133665 | GEO
Project description:<p>Most of pre-diabetes were eventually progress to diabetes, thereby profiling of prediabetic metabolic disorders may be an effective targeted preventive measure. We aimed to elucidate internal motivation of the progression of pre-diabetes to type 2 diabetes mellitus (T2DM) from a metabolic perspective. Four sets of serum samples (20 subjects per group) according to fasting blood glucose (FBG) concentration were collected for metabolomic analysis. An integrative approach of metabolome and WGCNA was employed to explore candidate metabolites. Compared with healthy group (FBG < 5.6 mmol/L), 113 metabolites were differentially expressed in the early stage of pre-diabetes (5.6 mmol/L ≤ FBG < 6.1 mmol/L), 237 in the late stage of pre-diabetes (6.1 mmol/L ≤ FBG < 7.0 mmol/L) and 245 in T2DM group (FBG ≥ 7.0 mmol/L). A total of 27 DEMs were identified shared in all comparisons. Among them, L-norleucine was down-regulated whereas ethionamide, glutathione oxidized, 5-Methylcytosine and alpha-D-Glucopyranoside beta-D-fructofuranosyl were increased with the rising of FBG. Surprisingly, 15 (11 LPCs, L-norleucine, glutathione oxidized, arachidonic acid and 5-Oxoproline) of the 27 DEMs were ferroptosis-associated metabolites. WGCNA clustered all metabolites into 8 modules and pathway enrichment analysis of DEMs showed a significant annotation to insulin resistance-related pathway. Integrated analysis of DEMs, ROC and WGCNA modules determined 12 potential biomarkers for pre-diabetes and T2DM, including L-norleucine, 8 of which were L-arginine or its metabolites. L-norleucine and L-arginine could be served as biomarkers for pre-diabetes. The inventory of metabolites provides by our serum metabolome offer insights into T2DM physiology metabolism.</p>
2024-04-29 | MTBLS8644 | MetaboLights
Project description:Objective: This study aims to establish a T2DM rat model consistent with the natural history of the disease, and apply TMT proteomics technology to analyze the retina to reveal the pathogenic mechanism of NPDR and search for new targets for NPDR intervention. Methods: Six-week-old SD male rats were randomly divided into type 2 diabetes group (T2DM group) and normal group (NOR group). T2DM group rats were fed with high-fat diet containing 60% fat energy, while NOR group rats were fed with normal chow diet. After 6 weeks, oral glucose tolerance tests were conducted on the two groups of rats. Following confirmation of insulin resistance, the T2DM group rats were intraperitoneally injected with 2% STZ (30mg/kg), and blood glucose levels were monitored 72 hours later. The rats with random blood glucose levels higher than 16.7 mmol/L were fed with the high-fat diet for another 6 weeks, and then retinas were collected from the two groups of rats for TMT proteomic analysis. Results: After 72 hours and 6 weeks after STZ injection, the T2DM group rats showed typical symptoms of diabetes such as hyperglycemia, weight loss, increased food intake and water consumption, suggesting the establishment of a rat model of T2DM. The bioinformatics analysis results of proteomics reveal the close relationship between differentially expressed proteins, fatty acid metabolism, and angiogenesis. Conclusion: In a T2DM rat model consistent with the natural history of the disease, this study used TMT proteomics technology to deeply analyze the molecular mechanism of NPDR and revealed the key role of fatty acid metabolism in the pathogenesis of NPDR. In addition, Fabp3, Tinagl1, Col4a3, and Snrpd1, may subserve candidate targets for NPDR intervention.
2025-05-07 | PXD056236 | Pride
Project description:Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with multiple etiologies, involving both genetic and environmental factors. With changes associated with modern life, increasing attention has been paid to chronic psychological stressors such as work stress. Chronic psychological stress can induce or aggravate diabetes mellitus, and conversely, with the deterioration of T2DM, patients often experience different degrees of depression, anxiety, and other negative emotions. To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the liver mitochondria-associated endoplasmic reticulum membrane proteome to improve T2DM with chronic psychological stress, differentially expressed proteins (DEPs) were identified among Zucker lean littermates (control group), chronic psychological stress T2DM rats (model group), and ZBPYR administration rats (ZBPYR group) via iTRAQ with LC-MS/MS. Using Mfuzz soft clustering analysis, DEPs were divided into six different clusters. Clusters 1-6 contained 5, 68, 44, 57, 28, and 32 DEPs, respectively. Given that ZBPYR can alleviate T2DM symptoms and affect exploratory behavior during T2DM with chronic psychological stress, we focused on the clusters with opposite expression trends between model:control and ZBPYR:model groups. We screened out the DEPs in clusters 1, 3, and 4, which may be good candidates for the prevention and treatment of T2DM with chronic psychological stress, and further conducted bioinformatics analyses. DEPs were mainly involved in the insulin signaling pathway, oxidative phosphorylation, tricarboxylic acid cycle, amino acid metabolism, lysosome-related processes, and lipid metabolism. This may indicate the pathogenic basis of T2DM with chronic psychological stress and the potential therapeutic mechanism of ZBPYR. In addition, two key proteins, a lysosome-associated protein (Lamp2) and tricarboxylic acid cycle-related protein (Suclg1), may represent novel biomarkers for T2DM with chronic psychological stress and drug targets of ZBPYR.
2022-10-25 | PXD029226 | Pride
Project description:Objective Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. Methods Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification.
2024-05-31 | GSE268372 | GEO
Project description:This study aims to explore the impact of type 2 diabetes mellitus (T2DM) on tear proteome, specifically investigating whether alterations occur before the development of diabetic retinopathy. Flush tear samples were collected from healthy subjects (n=13), subjects with preDM (n=16) and T2DM (n=18). Tear proteins were processed and analyzed by mass spectrometry-based shotgun proteomics using data independent acquisition parallel acquisition serial fragmentation (diaPASEF) approach. Machine learning algorithms, including random forest, lasso regression, and support vector machine, and statistical tools were used to identify biomarkers. Machine learning models identified 17 proteins with high importance in classification. Among these, five proteins (cystatin-S, S100-A11, submaxillary gland androgen-regulated protein 3B, immunoglobulin lambda variable 3-25 and lambda constant 3) exhibited differential expression across these three groups. No correlations were identified between proteins and clinical assessments of the ocular surface. Notably, the 17 important proteins identified by machine learning showed su-perior prediction accuracy in distinguishing all three groups (healthy, preDM, and T2DM) compared to the five proteins that were statistically differentially expressed. Alterations in tear proteome profile were observed in adults with preDM and T2DM before the clinical diagnosis of ocular abnormality including retinopathy.
2025-08-04 | PXD062366 | Pride
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. Insulin-treated T2DM subjects before and after 52 weeks of exercise training (T2DM_0 and T2DM_52), normoglycemic controls (NGT) and pre-diabetes subjects (IGT) and were selected. RNA was extracted from skeletal muscle biopsies and hybridized on Affymetrix microarrays.
2010-11-29 | E-GEOD-19420 | biostudies-arrayexpress
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2022-02-22 | PXD029337 | Pride
Project description:Purpose:The aim of this study was to investigate the potential effect of KeLuoXin on expression of miRNAs in DR with db/db mouse models Meathod: Six db/db mice of Group II were treated with 1560mg/kg KeLuoXin for 20 weeks, intragastrically, once a day, six model control mice were treated with equal volume normal saline.After 12 mice were sacrificed,retinal tissues were removed and stored in cryopreservation tubes. Total RNA was isolated from retina samples and used to prepare the miRNA sequencing library, The libraries were denatured as single-stranded DNA molecules, captured on Illumina flow cells, amplified in situ as clusters and finally sequenced for 51 cycles on Illumina NextSeq 500 according to the manufacturer's instruction. Raw sequencing data generated from Illumina NextSeq 500 that pass the Illumina chastity filter are used for following analysis. Differentially expressed miRNAs analyses were performed with R package edgeR. Fold change (cutoff 1.5), p-value (≤ 0.05) and CPM (≥ 1 mean in one group) were used for filtering differentially expressed miRNAs. Cluster analysis arranges samples into groups based on their expression level (CPM values), which allows us to hypothesize the relationships among samples. The heatmap were performed using significant differentially expressed miRNAs. The Scatter-Plot is a visualization method used for assessing the miRNA expression variation between the two compared groups.The Volcano plot is a visualization method for quick visual identification of miRNAs displaying large magnitude changes which are also statistically significant. MiRNA target prediction analysis for top 10 differentially expressed miRNAs were filtered based on miRNA target databases. Results: We obtained a total of 61,925,224 and 68,473,799 clean reads, 58,159,780 and 61,600,656 adapter-trimmed reads from the T2DM model group and KLX-treatment group. In detail, a total of 52 miRNAs up-regulated and 12 miRNAs were down-regulated in KLX-treatment group. The absolute fold changes ranged from 1.53 to 7.35 for up-regulated miRNAs, and from 0.020 to 0.008 for the down-regulated ones. The differential expression analysis identified 64 miRNAs that were differentially expressed from T2DM model group to KLX-treatment group and potently regulated by Keluoxin capsule. Up-regulated miRNAs targets were assigned to 45 categories (FDR<0.05, up-regulated miRNAs) as follows: 29 were associated with biological processes, 15 were associated with cellular components, 1 were involved in molecular functions. The KEGG pathways analysis indicated that the predicted targets of the miRNAs are involved in several important pathwayssuch as insulin secretion signaling pathway and TGF-beta signaling pathway. Conclusions: Keluoxin capsule may exert the retinal protection in T2DM by targeting miRNAs and regulating miRNAs-mediated signaling pathways downstream.
2022-02-25 | GSE128442 | GEO
Project description:Type 2 diabetes mellitus(T2DM)patients are a concern for dentists due to the lower success rate of healing period implant treatment. Here, we firstly calculated the success rate of in the healing period of diabetic and non-diabetic patients in the implant center of our hospital.Then we investigated the potential risk factors by proteomics analysis of 5 T2DM implant faliure patients in our implant center and compared the difference between high glucose induction study model and mesenchymal stem cell model from diabetic patients. The results suggested that the significantly higher implant failure rates in the T2DM group and the cell models derived from patients can be more comprehensive and accurate in reflecting the exact situation of BMSCs in patients with diabetes.
2021-11-02 | PXD016489 | Pride