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Status |
Public on Jan 26, 2009 |
Title |
Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low, intermediate and high [glucose] |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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Summary |
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
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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.
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Contributor(s) |
Bensellam M, Van Lommel L, Overbergh L, Schuit FC, Jonas JC |
Citation(s) |
19165461 |
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Submission date |
Sep 17, 2008 |
Last update date |
Jul 31, 2017 |
Contact name |
Jean-Christophe Jonas |
E-mail(s) |
Jean-Christophe.Jonas@uclouvain.be
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Phone |
+3227649575
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Fax |
+3227645532
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Organization name |
UCL, Faculty of Medicine
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Department |
Physiology and Pharmacology
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Lab |
Endocrinology and Metabolism
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Street address |
Av. Hippocrate, 55
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City |
Brussels |
ZIP/Postal code |
B-1200 |
Country |
Belgium |
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Platforms (1) |
GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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Samples (16)
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GSM322006 |
Pancreatic Islets_18h culture_2 mmol/l glucose_rep1 |
GSM322007 |
Pancreatic Islets_18h culture_2 mmol/l glucose_rep2 |
GSM322008 |
Pancreatic Islets_18h culture_2 mmol/l glucose_rep3 |
GSM322009 |
Pancreatic Islets_18h culture_2 mmol/l glucose_rep4 |
GSM322010 |
Pancreatic Islets_18h culture_5 mmol/l glucose_rep1 |
GSM322011 |
Pancreatic Islets_18h culture_5 mmol/l glucose_rep2 |
GSM322012 |
Pancreatic Islets_18h culture_5 mmol/l glucose_rep3 |
GSM322013 |
Pancreatic Islets_18h culture_5 mmol/l glucose_rep4 |
GSM322014 |
Pancreatic Islets_18h culture_10 mmol/l glucose_rep1 |
GSM322015 |
Pancreatic Islets_18h culture_10 mmol/l glucose_rep2 |
GSM322016 |
Pancreatic Islets_18h culture_10 mmol/l glucose_rep3 |
GSM322017 |
Pancreatic Islets_18h culture_10 mmol/l glucose_rep4 |
GSM322018 |
Pancreatic Islets_18h culture_30 mmol/l glucose_rep1 |
GSM322019 |
Pancreatic Islets_18h culture_30 mmol/l glucose_rep2 |
GSM322020 |
Pancreatic Islets_18h culture_30 mmol/l glucose_rep3 |
GSM322021 |
Pancreatic Islets_18h culture_30 mmol/l glucose_rep4 |
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Relations |
BioProject |
PRJNA111125 |
Supplementary file |
Size |
Download |
File type/resource |
GSE12817_RAW.tar |
66.3 Mb |
(http)(custom) |
TAR (of CEL, EXP) |
Processed data included within Sample table |
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