Epigenetic changes in Langerhans islets preceding the onset of diabetes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA601954 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10908200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10908200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10908201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10908201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10908202_1.fastq.gz | Fastqsanger.gz |
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Project description:Diabetes-resistant and diabetes-prone female New Zealand Obese mice were classified based on liver fat content and early blood glucose concentrations at 10 weeks of age before the onset of T2D. By using transcriptome and DNA methylome analysis of Langerhans islets, we identified early epigenetic alteration in mice and humans which could serve as putative epigenetic biomarkers
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Project description:The aim of this study was to investigate which intrinsic differences are present in the islets of Langerhans from diabetes-prone non-obese diabetic (NOD) mice before the onset of insulitis.
2016-11-30 | E-MTAB-5264 | biostudies-arrayexpress
Project description:The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62-0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.
| S-EPMC7576562 | biostudies-literature
Project description:NOD mice deficient in the transcription factor Batf3 never develop diabetes. The goal of this study was to determine if NOD.Batf3-/- mice islets had any inflammatory signature associated with type 1 diabetes. Islets of Langerhans were isolated from NOD, NOD.Batf3-/-, and NOD.Rag1-/- and then compared to determine inflammatory gene profiles. At 6 and 8 weeks of age, NOD.Batf3-/- islets had an absence of inflammatory gene expression and were almost identical to uninflamed NOD.Rag1-/- islets. This work shows that absence of the Batf3 transcription factor is sufficient to prevent all the inflammatory sequelae of autoimmune diabetes. RNA was isolated from the pancreatic islets of Langerhans of 27 experimental mice. Mice were aged either 6 or 8 weeks. Three genotypes were tested: NOD, NOD.Rag1-/-, and NOD.Batf3-/-. There were 3-6 biological replicates per condition. All mice were female. All data was normalized using RMA in Arraystar.
2014-09-29 | E-GEOD-61847 | biostudies-arrayexpress
Project description:NOD mice deficient in the transcription factor Batf3 never develop diabetes. The goal of this study was to determine if NOD.Batf3-/- mice islets had any inflammatory signature associated with type 1 diabetes. Islets of Langerhans were isolated from NOD, NOD.Batf3-/-, and NOD.Rag1-/- and then compared to determine inflammatory gene profiles. At 6 and 8 weeks of age, NOD.Batf3-/- islets had an absence of inflammatory gene expression and were almost identical to uninflamed NOD.Rag1-/- islets. This work shows that absence of the Batf3 transcription factor is sufficient to prevent all the inflammatory sequelae of autoimmune diabetes.
2014-09-29 | GSE61847 | GEO
Project description:Diabetes results from insufficient insulin secretion as a result of dysfunction to β-cells within the islet of Langerhans. Elevated glucose causes β-cell membrane depolarization and action potential generation, voltage gated Ca2+ channel activation and oscillations in free-Ca2+ activity ([Ca2+]), triggering insulin release. Nuclear Factor of Activated T-cell (NFAT) is a transcription factor that is regulated by increases in [Ca2+] and calceineurin (CaN) activation. NFAT regulation links cell activity with gene transcription in many systems, and within the β-cell regulates proliferation and insulin granule biogenesis. However the link between the regulation of β-cell electrical activity and oscillatory [Ca2+], with NFAT activation and downstream transcription is poorly understood. In this study we test whether dynamic changes to β-cell electrical activity and [Ca2+] regulates NFAT activation and downstream transcription. In cell lines, mouse islets and human islets, including those with type2 diabetes, we applied both agonists/antagonists of ion channels together with optogenetics to modulate β-cell electrical activity. Both glucose-induced membrane depolarization and optogenetic-stimulation triggered NFAT activation, and increased transcription of NFAT targets and intermediate early genes (IEGs). Importantly only conditions in which slow sustained [Ca2+] oscillations were generated led to NFAT activation and downstream transcription. In contrast in human islets from donors with type2 diabetes NFAT activation by glucose was diminished, but rescued upon pharmacological stimulation of electrical activity. Thus, we gain insight into the specific patterns of electrical activity that regulate NFAT activation and gene transcription and how this is disrupted in diabetes.
2020-06-23 | GSE152970 | GEO
Project description:The spatial architecture of the islets of Langerhans is hypothesized to facilitate synchronized insulin secretion among β cells, yet testing this in vivo in the intact pancreas is challenging. Robo βKO mice, in which the genes Robo1 and Robo2 are deleted selectively in β cells, provide a unique model of altered islet spatial architecture without loss of β cell differentiation or islet damage from diabetes. Combining Robo βKO mice with intravital microscopy, we show here that Robo βKO islets have reduced synchronized intra-islet Ca2+ oscillations among β cells in vivo. We provide evidence that this loss is not due to a β cell-intrinsic function of Robo, mis-expression or mis-localization of Cx36 gap junctions, or changes in islet vascularization or innervation, suggesting that the islet architecture itself is required for synchronized Ca2+ oscillations. These results have implications for understanding structure-function relationships in the islets during progression to diabetes as well as engineering islets from stem cells.
2024-08-26 | GSE275474 | GEO
Project description:Type 2 diabetes is a worldwide disease reaching epidemic dimensions. The rapid progression of the disease urgently calls for both a broader and deeper understanding of its pathophysiology. In line with this statement, the Human Diabetes Proteome Project (HDPP) was officially launched at the 11th HUPO meeting in Boston, 2012. A special session was dedicated to this new initiative, gathering experts in the main topics related to diabetes and its associated complications. Key issues were debated with a focus on how deranged circulating glucose and free fatty acids induce dysfunction. It has been decided that HDPP will therefore focus on studying the early stages of diabetes that lead to abnormal glucose and lipid levels. The initiative will initially focused on islets of Langerhans, insulin-producing cell lines, and blood human samples from diabetes-related cohorts. In subsequent stages HDPP will investigate target tissues in which glucose and lipids could promote protein dysfunctions. Omics-rooted systems approaches enhanced by bioinformatics will be deployed to unravel effects of lipids and glucose triggering diabetes initiation and progression. A first milestone has been defined for the 12th HUPO meeting in Yokohama, 2013: the 1000 diabetes-associated protein (the 1000-HDPP) database, i.e. a freely available internet resource (www.HDPP.info) of more than 1000 proteins with links to their corresponding proteotypic peptides, affinity reagents and protein-specific biological/biomedical information. Human islets digested and seperated by off-gel electrophoresis. Analysis by LTQ-Orbitrap velos mass spectrometer (fragmentation by CID,gaz phase fractionnation with four m/z windows: 400-520, 515-690, 685-979, 974-2000)
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Project description:Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin producing beta cells. We characterized the gene expression profile of pancreatic tissue from four type 1 diabetes patients (Cases 1-4), who died at different stages of the disease (onset and longstanding) by microarray analysis. All samples from patients and controls were obtained after death, at the time of organ donation. Pancreatic blocks from the four diabetic patients and three organ donors (Controls 1-3) were obtained and snap frozen. At the same time, islets from Cases 1 and 4 were isolated from a piece of the pancreas tail by enzymatic digestion (using automated method and handpicking) and snap frozen. Islets from three different organ donors (Controls 4-6) were obtained similarly to those of the diabetic patients. Both pancreatic blocks and islets were stored in liquid nitrogen until the mRNA extraction. For pancreas gene expression profiles, we compared data from three blocks of each of the four type 1 diabetic pancreas with pancreases data from the Controls 1-3. For islets expression profile, we compared data from Cases 1 and 4 islets with islets data from the Controls 4-6. <br><br>
2009-12-01 | E-MEXP-1140 | biostudies-arrayexpress
Project description:Type 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the β-cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research. 57 RNA samples isolated from the pancreatic islets of langerhans of experimental mice: 2-18 wk old non-obese diabetic (NOD) and newly diabetic NOD were compared to controls: NOD.RAG-/-, B6.g7 and C57BL/6. There were 3 or 6 biological replicates per condition. All mice were female. All data was normalized using RMA in Arraystar. Data table includes normalized probe intensity for every probe.
2013-01-28 | E-GEOD-41203 | biostudies-arrayexpress