Beta cells (MIN6) treated with amylin at different times and doses and growth at different concentrations of glucose
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE2253 | GEO | 2005/04/12
SECONDARY ACCESSION(S): PRJNA91357
REPOSITORIES: GEO
Similar Datasets
Project description:Murine pancreatic beta cell line MIN6 was growth at two different concentrations of glucose (22,2 and 5,5 mM of glucose), 37ºC, 5% CO2 and was treated at four different concentrations of human amylin (0, 1, 10 and 20 uM) during three different times (2, 12 and 24 hours)
2009-04-10 | E-GEOD-2253 | biostudies-arrayexpress
Project description:M-NM-2-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring M-NM-2-cell adaptation to the organismM-bM-^@M-^Ys insulin demands. We have observed in pancreatic islets that stimulatory glucose concentrations induced a gene profile that was similar to that of freshly isolated islets, indicating that glucose-elicited cues are involved in maintaining M-NM-2-cell identity. Low glucose induces the expression of ubiquitous genes involved in stress responses, nutrient sensing, and organelle biogenesis. By contrast, stimulatory glucose concentrations activate genes with a more restricted expression pattern (M-NM-2- and neuronal- cell identity). Consistently, glucose-induced genes are globally reduced in islets deficient with Hnf1a (MODY3), characterized by a deficient glucose metabolism. Of interest, a cell cycle gene module was the most enriched among the variable genes between intermediate and stimulatory glucose concentrations. Glucose regulation of the islet transcriptome was unexpectedly broadly maintained in islets from aged mice. However, the cell cycle gene module is selectively lost in old islets and the glucose activation of this module is not recovered even in the absence of the cell cycle inhibitor p16. We used microarrays to detail the global programme of gene expression regulated by glucose in young and aged pancreatic islets as well as freshly-isolated islets. Pancreatic islets from young and old mice were isolated and cultured at different glucose concentrations for RNA extraction and hybridization on Affymetrix microarrays. Islets were cultured at 3mM (G3), 5.5mM (G5), 11mM (G11) and 16mM (G16). Freshly-isolated islets (F) were also processed for RNA extraction . We also assessed the dynamic glucose regulation of gene expression at different time-points after an overnight at 3mM (T0): after 1h at 11mM (T1) and after 4h (T4).
2013-07-01 | E-GEOD-42591 | biostudies-arrayexpress
Project description:Beta cells (MIN6) treated with amylin at different times and doses and growth at different concentrations of glucose
| PRJNA91357 | ENA
Project description:β-cell identity is determined by tightly regulated transcriptional networks that are modulated by extracellular cues, thereby ensuring β-cell adaptation to the organism’s insulin demands. We have observed in pancreatic islets that stimulatory glucose concentrations induced a gene profile that was similar to that of freshly isolated islets, indicating that glucose-elicited cues are involved in maintaining β-cell identity. Low glucose induces the expression of ubiquitous genes involved in stress responses, nutrient sensing, and organelle biogenesis. By contrast, stimulatory glucose concentrations activate genes with a more restricted expression pattern (β- and neuronal- cell identity). Consistently, glucose-induced genes are globally reduced in islets deficient with Hnf1a (MODY3), characterized by a deficient glucose metabolism. Of interest, a cell cycle gene module was the most enriched among the variable genes between intermediate and stimulatory glucose concentrations. Glucose regulation of the islet transcriptome was unexpectedly broadly maintained in islets from aged mice. However, the cell cycle gene module is selectively lost in old islets and the glucose activation of this module is not recovered even in the absence of the cell cycle inhibitor p16. We used microarrays to detail the global programme of gene expression regulated by glucose in young and aged pancreatic islets as well as freshly-isolated islets.
2013-07-01 | GSE42591 | GEO
Project description:There is a need for greater understanding of the molecular mechanism underlying the development of insulin resistance in type 2 diabetes, and new models in which to study this. The hormone amylin is postulated to be involved in the development of this disease, as human amylin (hA) forms amyloid in the pancreases of diabetic patients, and wild-type hA oligomers have been shown to be cytotoxic to β-cells. By contrast, rodent amylin is non-amyloidogenic, so mice expressing wild-type hA have been developed. However, amylin-evoked β-cell loss in these models limits the secretion of amylin and insulin. We have developed transgenic mice that overexpress [25, 28, 29triprolyl]human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 (L44) model. These mice develop obesity and hyperglycaemia. We examined the expression of 43 genes involved in amylin, insulin and leptin signalling in the brain of this model, at different disease stages, using the NanoString nCounter (NanoString Technologies, Seattle, WA, USA). After onset of diabetes, mice remained hyperglycaemic for a period of time but blood glucose levels eventually returned to normoglycaemia. The incidence of diabetes (defined as having blood glucose measurements > 11 mM over 3 consecutive weeks) was gene-dose dependent; 81% of homozygous mice and 59% of hemizygous mice developed diabetes over 400 days. A proportion of nontransgenic mice (33%) also developed diabetes. As these were bred from hemizygous pairs this may be the result of epigenetic or environmental factors.
2019-10-10 | GSE132940 | GEO
Project description:Variants close to the VPS13C/C2CD4A/C2CD4B locus are associated with altered risk of type 2 diabetes in genome-wide association studies. Whilst previous functional work has suggested roles for VPS13C and C2CD4A in disease development, none has explored the role of C2CD4B. Here, we show that systemic inactivation of C2cd4b in mice leads to marked, but highly sexually dimorphic, changes in body weight and glucose homeostasis. Female C2cd4b mice display unchanged body weight but abnormal glucose tolerance and defective in vivo, but not in vitro, insulin secretion, associated with a marked decrease in follicle stimulating hormone levels. In sharp contrast, male C2cd4b null mice displayed normal glucose tolerance but an increase in body weight and fasting glycemia after maintenance on high fat diet. No metabolic disturbances were observed after global inactivation of C2cd4a in mice, or in pancreatic β cell function at larval stages in C2cd4ab null zebrafish. These studies suggest that C2cd4b may act centrally to influence sex-dependent circuits which control pancreatic β cell function and glucose tolerance in rodents. However, the absence of sexual dimorphism in the impact of diabetes risk variants argues for additional roles for C2CD4A or VPS13C in the control of glucose homeostasis in man.
2020-11-16 | PXD021597 | Pride
Project description:To investigate the effect of pancreatic human amylin protein on the gene expression profiles of the brain
2022-12-25 | GSE221450 | GEO
Project description:Comparative gene expression in NCI-H716 cells grown in different glucose concentrations
| PRJNA562299 | ENA
Project description:Although persistent elevations in circulating glucose concentrations promote compensatory increases in pancreatic islet mass, unremitting insulin resistance causes a deterioration in beta cell function that disrupts glucose balance and signals the progression to diabetes 1. Glucagon like Peptide 1 (GLP1) agonists improve glucose tolerance in insulin resistance, although some individuals are unresponsive to treatment. Here we show that increases in GLP1 during feeding promote beta cell function in part through the PKA-mediated activation of CREB and its coactivator CRTC2 2. Mice with a knockout of CRTC2 in beta cells have impaired oral glucose tolerance due to decreases in circulating insulin concentrations. CRTC2 was found to promote beta cell function in part by stimulating the expression of the transcription factor MafA. Chronic hyperglycemia associated with high fat or high carbohydrate diet feeding disrupted cAMP signaling in pancreatic islets. Indeed, prolonged elevations in circulating glucose concentrations interfered with CREB signaling by activating the mTOR pathway and triggering the hypoxia inducible factor (HIF1)-dependent induction of the Protein Kinase A Inhibitor beta (PKIB), a potent inhibitor of PKA catalytic activity 3. As disruption of the PKIB gene restored glucose tolerance and insulin secretion in obesity, our results demonstrate how cross-talk between nutrient and hormonal pathways contributes to loss of pancreatic islet function in insulin resistance. Rat insulinoma cells were used to interrogate the impact of glucose exposure and CREB activity on cAMP dependent gene regulation in the pancreatic beta cells
2015-02-23 | E-GEOD-60158 | biostudies-arrayexpress
Project description:Selenium is an essential trace element that has gained interest for its potential role in glucose homeostasis. The purpose of the present study was to investigate the impact of selenium supplementation as selenomethionine (SeMet) on insulin secretion in MIN6-K8 cells, a model of pancreatic -cells. We found that 40 μM and 80 μM SeMet significantly enhanced percent insulin secretion at low (2.8 mM), intermediate (11.7 mM), and high (16.7 mM) glucose stimulation. SeMet also increased tolbutamide- or KCl-induced percent insulin secretion at 40 μM and 80 μM. Ca2+ influx was only reduced with 80 μM SeMet. RNA-sequencing showed that 40 μM SeMet supplementation upregulated expression of selenoprotein H (SelH) and thioredoxin reductase 1 (Txnrd 1) and downregulated expression of glutathione peroxidase 3 (Gpx3), selenoprotein O (SelO), and selenoprotein P (SelP). Gpx3 knockdown increased both percent and total insulin release with high glucose stimulation. SelP knockdown increased insulin release at high glucose. In conclusion, high SeMet supplementation augments insulin secretion, while reductions in Gpx3 and SelP expression, from SeMet supplementation or via silencing, augment -cell function in the MIN6-K8 cell line. These studies support a putative role for selenium and selenoproteins in the regulation of glucose homeostasis and diabetes risk.
2024-03-13 | GSE183775 | GEO