Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA111125 | ENA |
REPOSITORIES: ENA
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Project description:Background: Survival and function of insulin-secreting pancreatic β-cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2mM glucose improves rodent β-cell survival and function whereas glucose concentrations above 10mM are deleterious. Aim-Method: To identify the mechanisms of such β-cell plasticity, we tested the effects of a 18h culture at 2, 5, 10 and 30mM glucose on the transcriptome of rat islets precultured for 1 week at 10mM glucose (Affymetrix Rat 230.2 arrays). Results: Culture in either 2-5mM or 30mM instead of 10mM glucose markedly impaired β-cell function without affecting islet cell survival. Of ~16000 probe sets reliably detected in islets, ~5000 were significantly regulated at least 1.4-fold by glucose. Analysis of these probe sets with GeneCluster software identified 10 mRNA profiles with unidirectional up- or down-regulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mM glucose, and 8 complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10mM glucose. Analysis of genes belonging to these various clusters with Onto-express and GenMapp software revealed several signaling and metabolic pathways that may contribute to the induction of β-cell dysfunction and apoptosis after culture in low or high vs. intermediate glucose concentration. Conclusion: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understanding the mechanisms by which glucose affects β-cell survival and function under states of chronic hypo- or hyperglycemia. Experiment Overall Design: Effect of 18h culture in 2, 5, 10 and 30 mmol/l glucose on the transcriptome of rat pancreatic islets precultured for 1 week in 10 mmol/l glucose. Four experiments were done on different islet preparations over a two-months period.
2009-01-31 | E-GEOD-12817 | biostudies-arrayexpress
Project description:Background: Survival and function of insulin-secreting pancreatic β-cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2mM glucose improves rodent β-cell survival and function whereas glucose concentrations above 10mM are deleterious. Aim-Method: To identify the mechanisms of such β-cell plasticity, we tested the effects of a 18h culture at 2, 5, 10 and 30mM glucose on the transcriptome of rat islets precultured for 1 week at 10mM glucose (Affymetrix Rat 230.2 arrays). Results: Culture in either 2-5mM or 30mM instead of 10mM glucose markedly impaired β-cell function without affecting islet cell survival. Of ~16000 probe sets reliably detected in islets, ~5000 were significantly regulated at least 1.4-fold by glucose. Analysis of these probe sets with GeneCluster software identified 10 mRNA profiles with unidirectional up- or down-regulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mM glucose, and 8 complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10mM glucose. Analysis of genes belonging to these various clusters with Onto-express and GenMapp software revealed several signaling and metabolic pathways that may contribute to the induction of β-cell dysfunction and apoptosis after culture in low or high vs. intermediate glucose concentration. Conclusion: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understanding the mechanisms by which glucose affects β-cell survival and function under states of chronic hypo- or hyperglycemia. Keywords: Dose response
2009-01-26 | GSE12817 | GEO
Project description:Glucose culture effects on mouse pancreatic islet
| PRJNA1090876 | ENA
Project description:Islet mRNA changes in rat pancreatic islets during aging
| PRJNA294102 | ENA
Project description:PPAR gamma overexpression and activation in rat pancreatic islet
| PRJNA91989 | ENA
Project description:Islet microRNA changes in the rat pancreatic islets during aging
| PRJNA294101 | ENA
Project description:C57BLKS/J mice are susceptible to diabetes, because of islet dysfunction, whereas C57BL6/J mice are not. Differences in gene expression between the two strains may account for this sensitivity. Furthermore these differences may only be evident in the hyperstimulated (diabetic or hyperglycemic) state. To this end profiling islets from these two strains cultured in both low and high glucose may reveal the underlying mechanism. Keywords: Mouse strain comparison under different culture conditions In the study presented here, pancreatic islets from 20 mice grown in low and high glucose conditions were assayed for differences in gene expression. (five C57BLKS/J low glucose, four C57BLKS/J high glucose, six C57BL6/J low glucose, five C57BL6/J high glucose). Technical replicates are achieved by labeling each sample with both Cy3 and Cy5, and combining the values for each hybridization.
2008-12-30 | E-GEOD-11257 | biostudies-arrayexpress
Project description:Here we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
2014-07-17 | E-GEOD-50244 | biostudies-arrayexpress
Project description:Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1-Cre;Sirt1(ex4F/F) mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1-Cre;Sirt1(ex4F/F) mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2A2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as with a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncover a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted. To uncover other Sirt1-regulated mechanisms, we performed a gene expression microarray analysis comparing pancreata from the 6 month old Sirt1âdeficient mice to their controls (n=3 per group).
2016-03-01 | E-GEOD-67239 | biostudies-arrayexpress
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