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Status |
Public on Jan 03, 2017 |
Title |
Biological characterization of gene response to insulin-induced hypoglycemia in mouse retina |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Glucose is the most important metabolic substrate of the retina and maintenance of nor-moglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. We recently showed that hy-poglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression is modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we highlight, by gene set enrichment analysis, three important pathways, including KEGG lysosomes, KEGG GSH metabolism and REACTOME apoptosis pathways. We tested the effect of recurrent hypoglycemia (three successive 5h periods of hypoglycemia separated by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevents retinal cell death and GSH decrease, or adapts the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining “normal” GSH level, as well as a strict glycemic control, may represent a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.
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Overall design |
4 experimental groups, 3 samples per group
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Contributor(s) |
Emery M, Nanchen N, Ibberson M, Preitner F, Thorens B, Schorderet DF, Roduit R |
Citation(s) |
26918849 |
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Submission date |
Apr 02, 2015 |
Last update date |
Jan 04, 2017 |
Contact name |
Mark Ibberson |
Organization name |
SIB Swiss Institute of Bioinformatics
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Department |
Vital-IT
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Street address |
Genopode building
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City |
Lausanne |
ZIP/Postal code |
CH-1015 |
Country |
Switzerland |
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Platforms (1) |
GPL10740 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [probe set (exon) version] |
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Samples (12)
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GSM1648752 |
Retina, 4 hours, hypoglycemic clamp, replicate 1 |
GSM1648753 |
Retina, 4 hours, hypoglycemic clamp, replicate 2 |
GSM1648754 |
Retina, 4 hours, hypoglycemic clamp, replicate 3 |
GSM1648755 |
Retina, 4 hours, euglycemic clamp, replicate 1 |
GSM1648756 |
Retina, 4 hours, euglycemic clamp, replicate 2 |
GSM1648757 |
Retina, 4 hours, euglycemic clamp, replicate 3 |
GSM1648758 |
Retina, 48 hours, hypoglycemic clamp, replicate 1 |
GSM1648759 |
Retina, 48 hours, hypoglycemic clamp, replicate 2 |
GSM1648760 |
Retina, 48 hours, hypoglycemic clamp, replicate 3 |
GSM1648761 |
Retina, 48 hours, euglycemic clamp, replicate 1 |
GSM1648762 |
Retina, 48 hours, euglycemic clamp, replicate 2 |
GSM1648763 |
Retina, 48 hours, euglycemic clamp, replicate 3 |
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Relations |
BioProject |
PRJNA280156 |
Supplementary file |
Size |
Download |
File type/resource |
GSE67523_RAW.tar |
48.7 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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