MicroRNA Expression in Normal and Diabetic Pancreatic Islets
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ABSTRACT:
PROVIDER: PRJNA807330 | ENA |
REPOSITORIES: ENA
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Project description:Human pancreatic islets isolated from 7 people with normal glucose tolerance, and 5 people with type 2 diabetes. All 12 people were organ donors after either cerebrovascular accident or intracerebral haemorrhage. Normals were required to maintain glucose at least 6.1mM in intensive care. Diabetic subjects were all at least 10 years from diagnosis and not insulin-requiring. For every subject, RNA was isolated, cRNA was made and hybridized to the U133A and U133B Affymetrix arrays (total of 24 arrays). No samples were pooled.
2009-07-28 | E-CBIL-20 | biostudies-arrayexpress
Project description:Genetic studies have identified ≥240 loci associated with type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating gene expression in pancreatic islets have provided key insights into the molecular drivers of T2D pathophysiology through comprehensive genetic and genomic analyses. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present the largest genetic and genomic analysis of miRNA expression in human islets to date, spanning 63 participants. We characterize the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into cis- and trans- genetic components and mapping cis loci associated with miRNA expression (miRNA-eQTLs). We find (a) 81 heritable miRNAs, which we show are primarily regulated by trans-acting genetic effects, and (b) 5 miRNA-eQTLs. To evaluate the impact of miRNA expression on T2D, we use several different strategies to nominate T2D-associated miRNAs. First, we colocalize miRNA-eQTLs with genetic studies of T2D and several T2D-related traits and identify one miRNA, miR-1908, that shares genetic signals for blood glucose and HbA1c. Next, we intersect miRNA seed regions with credible set SNPs from T2D and T2D-related genetic studies and find 46 miRNAs that may have altered binding and function due to disrupted seed regions. Finally, we perform differential expression analysis and identify 38 miRNAs associated with either T2D status, body mass index, sex, or a polygenic score for HbA1c levels. To validate identified miRNAs, we perform chromatin run-on sequencing and confirm differential transcription of T2D-associated miRNAs.
2023-01-29 | GSE196797 | GEO
Project description:Little is known about the contribution of the epigenome to the pathophysiology of type 2 diabetes (T2D). Here we have used genome-wide DNA methylation profiling to obtain the first comprehensive DNA methylation data set for human T2D pancreatic islets. Therefore, we analyzed the methylation profile of 27,578 CpG sites affiliated to more than 14,000 genes in 16 samples of pancreatic islets, 11 normal and 5 type 2-diabetic. Keywords: DNA methylation Keywords: Methylation profiling by array We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA BeadChip array) in genomic DNA obtained from pnacreatic islets of 11 non-diabetic and 5 type-2-diabetic male human donors to identify genes that are differentially methylated in T2D.
2012-04-22 | E-GEOD-21232 | biostudies-arrayexpress
Project description:We have studied the impact of T2D on open chromatin in human pancreatic islets. We used assay for transposase-accessible chromatin using sequencing (ATAC-seq) to profile open chromatin in islets from T2D and non-diabetic donors. We identified ATAC-seq peaks representing open chromatin regions in islets of non-diabetic and diabetic donors. The majority of ATAC-seq peaks mapped near transcription start sites. Additionally, peaks were enriched in enhancer regions and in regions where islet-specific TFs bind. Islet ATAC-seq peaks overlap with SNPs associated with T2D and with additional SNPs in LD with known T2D SNPs. There was enrichment of open chromatin regions near highly expressed genes in human islets.
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Project description:Investigation of gene expression level changes in pancreatic and liver tissues of diabetic db/db mice supplemented with selenate, compared to the diabetic db/db mice administered placebo. Fasting blood glucose levels increased continuously in diabetic db/db mice administered placebo (DMCtrl) but decreased gradually in selenate-supplemented diabetic db/db mice (DMSe) and approached normal values when the experiment ended. The size of pancreatic islets increased, causing the plasma insulin concentration to double in DMSe mice compared with that in DMCtrl mice. Two six chip studies using total RNA respectively isolated from pancreatic and liver tissues of three selenate-supplemented diabetic db/db mice, and three diabetic db/db mice administered placebo.
2014-03-07 | E-GEOD-55636 | biostudies-arrayexpress
Project description:Human pancreatic islets were isolated from pancreas of deceased donors by Ricordi's procedure and cultured in CMRL 1066 medium additioned with human albumin. EVs were isolated from conditioned medium derived from islet culture after isolation. Once isolated, RNA of islets and islet-derived EVs was extracted and analyzed for microRNA expression within 48 hours after isolation.
2012-07-30 | E-MEXP-3691 | biostudies-arrayexpress
Project description:Little is known about the contribution of the epigenome to the pathophysiology of type 2 diabetes (T2D). Here we have used genome-wide DNA methylation profiling to obtain the first comprehensive DNA methylation data set for human T2D pancreatic islets. Therefore, we analyzed the methylation profile of 27,578 CpG sites affiliated to more than 14,000 genes in 16 samples of pancreatic islets, 11 normal and 5 type 2-diabetic. Keywords: DNA methylation Keywords: Methylation profiling by array
2012-04-23 | GSE21232 | GEO
Project description:Investigation of gene expression level changes in pancreatic and liver tissues of diabetic db/db mice supplemented with selenate, compared to the diabetic db/db mice administered placebo. Fasting blood glucose levels increased continuously in diabetic db/db mice administered placebo (DMCtrl) but decreased gradually in selenate-supplemented diabetic db/db mice (DMSe) and approached normal values when the experiment ended. The size of pancreatic islets increased, causing the plasma insulin concentration to double in DMSe mice compared with that in DMCtrl mice.
2014-03-07 | GSE55636 | GEO