Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA252782 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes
| PRJNA252758 | ENA
Project description:The microRNA-200 family regulates pancreatic beta-cell survival in type 2 diabetes (islet)
| PRJNA252783 | ENA
Project description:Transcriptional and posttranscriptional regulatory networks play a crucial role in the maintenance and adaptation of pancreatic beta-cell function. In this study we show that the levels of the prototypic neuroendocrine miRNA-7 are regulated in islets of obese, diabetic and aged mouse models. Using gain- and loss-of-function models we demonstrate that miR-7 regulates crucial members of the endocrine pancreatic transcriptional network controlling differentiation and insulin synthesis. Importantly, it also directly regulates key proteins in the insulin granule secretory machinery. These results reveal an interconnecting miR-7 genomic circuit that influences beta-cell differentiation, insulin synthesis and release and define a role for miR-7 as an endocrine checkpoint to stabilize beta-cell function during metabolic stress. These findings have implications for miR-7 inhibitors as potential therapies for type 2 diabetes and neurodegenerative diseases. Either miR-7a2 or miR-7b were over-expressed in MIN6 cells using an adenoviral vector. The miR-7a infection was performed in duplicates. In addition, a GFP over-expression in MIN6 using the same viral vector served as control. We also explored the consequence of miR-7a2 deletion in pancreatic beta-cells by generating a beta-cells specific miR-7a2 knock-out using the Lox/Cre system in a C57BL/6 background. We profiled gene expression in mutant and wild-type (control) islets.
2015-06-30 | E-GEOD-48195 | biostudies-arrayexpress
Project description:Stat5b gene is located at IDD4 type 1 diabetes susceptibility interval, and is mutated in NOD mice. This mutation has been linked to diabetes with strong association with autoimmune aetiology. We have treated MIN6 pancreatic beta cell line with Stat5b siRNA and analyzed the differential expression profile in control siRNA treated versus Stat5b siRNA treated cells in an effort to understand the role of Stat5b in diabetes.
2022-12-31 | GSE85496 | GEO
Project description:Recent studies have identified dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing in the onset of diseases including diabetes. Here we investigated the role of RBFOX2 in the pancreatic β cell through the conditional mutation of Rbfox2 in the mouse pancreas (Pdx1:Cre; Rbfox2fl/lf) and RNAi experiments in the mouse insulinoma cell line, MIN6. We then identified the direct targets of RBFOX2 in the mouse β cell transcriptome my eCLIP-Seq in MIN6 cells.
2023-09-25 | GSE221274 | GEO
Project description:Recent studies have identified dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing in the onset of diseases including diabetes. Here we investigated the role of RBFOX2 in the pancreatic β cell through the conditional mutation of Rbfox2 in the mouse pancreas (Pdx1:Cre; Rbfox2fl/lf) and RNAi experiments in the mouse insulinoma cell line, MIN6. We then identified the direct targets of RBFOX2 in the mouse β cell transcriptome my eCLIP-Seq in MIN6 cells.
2023-09-25 | GSE221276 | GEO
Project description:Recent studies have identified dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing in the onset of diseases including diabetes. Here we investigated the role of RBFOX2 in the pancreatic β cell through the conditional mutation of Rbfox2 in the mouse pancreas (Pdx1:Cre; Rbfox2fl/lf) and RNAi experiments in the mouse insulinoma cell line, MIN6. We then identified the direct targets of RBFOX2 in the mouse β cell transcriptome my eCLIP-Seq in MIN6 cells.
2023-09-25 | GSE221275 | GEO
Project description:HNF1A gene encodes a transcription factor hepatocyte nuclear factor 1α (HNF1α), and mutations in this gene cause maturity-onset diabetes of the young type 3 (MODY3), which is characterized by impaired insulin secretion. Previous studies have shown that HNF1α controls the proliferation and number of pancreatic β-cells. However, the molecular mechanism by which HNF1α regulates β-cell growth remains unclear. Here, we demonstrate that TMED6 (transmembrane p24 trafficking protein 6), a transmembrane protein involved in transport processes at the ER-Golgi interface, is a novel HNF1α target in pancreatic β-cells. TMED6 expression was decreased in the β-cells of Hnf1a knockout (KO) mice. Suppressing TMED6 in mouse MIN6 β-cells reduced cell growth. Conversely, overexpression of TMED6 rescued the proliferation of Hnf1a knockdown (KD) MIN6 cells. Furthermore, TMED6 KO mice fed a high-fat diet exhibited reduced β-cell mass and impaired insulin secretion. Biochemical studies revealed that TMED6 controls β-cell proliferation by regulating the proteasomal degradation of GOLGA2, a Golgi-associated protein that regulates cell proliferation. Overexpression of GOLGA2 restored proliferation in both Hnf1a KD and Tmed6 KD MIN6 cells. Taken together, our results indicate that HNF1α controls pancreatic β-cell proliferation via the TMED6-GOLGA2 axis.
We performed proteome analyses of control and Tmed6 KD MIN6 cells in triplicate.
2026-07-09 | PXD065932 | JPOST Repository
Project description:Pancreatic beta cells have well-developed endoplasmic reticulum (ER) to accommodate for the massive production and secretion of insulin. ER homeostasis is vital for normal beta cell function. Perturbation of ER homeostasis contributes to beta cell dysfunction in both type 1 and type 2 diabetes. To systematically identify the molecular machinery responsible for proinsulin biogenesis and maintenance of beta cell ER homeostasis, a widely used mouse pancreatic beta cell line, MIN6 cell was used to purify rough ER. Two different purification schemes were utilized. In each experiment, the ER pellets were solubilized and analyzed by one dimensional SDS-PAGE coupled with HPLC-MS/MS. A total of 1467 proteins were identified in three experiments with ≥95% confidence, among which 1117 proteins were found in at least two separate experiments. Gene ontology analysis revealed a comprehensive profile of known and novel players responsible for proinsulin biogenesis and ER homeostasis. This dataset defines a molecular environment in the ER for proinsulin synthesis, folding and export and laid a solid foundation for further characterizations of altered ER homeostasis under diabetes-causing conditions.
2015-04-15 | PXD001081 | Pride