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| Status |
Public on Nov 19, 2012 |
| Title |
The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
AIMS/HYPOTHESIS: Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function.
METHODS: Rkip1 (also known as Pebp1) knockout (Rkip1 (-/-)) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 (-/-) mice after streptozotocin treatment.
RESULTS: Rkip1 (-/-) mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 (-/-) mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice.
CONCLUSIONS/INTERPRETATION: These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.
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| Overall design |
Pancreatic gene expression of Rkip-1 (Raf kinase inhibitor 1) knockout (KO) and wild type (WT) mice, including three biological replicates in each group.
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| Contributor(s) |
Pardo FN, Altirriba J, Pradas-Juni M, García A, Ahlgren U, Barberà A, Slebe JC, Yañez A, Gomis R, Gasa R |
| Citation(s) |
22926403 |
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| Submission date |
Aug 02, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Jordi Altirriba |
| E-mail(s) |
altirriba@hotmail.com
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| Organization name |
Centre Médical Universitaire de Genève
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| Department |
Dpts de Médecine Interne et de Physiologie cellulaire et Métabolisme
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| Lab |
Laboratoire du Métabolisme
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| Street address |
Rue Michel-Servet 1
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| City |
Genève |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM771022 |
Pancreas from adult Rkip-1 KO mice, biological replicate 1 |
| GSM771023 |
Pancreas from adult Rkip-1 KO mice, biological replicate 2 |
| GSM771024 |
Pancreas from adult Rkip-1 KO mice, biological replicate 3 |
| GSM771025 |
Pancreas from adult WT mice, biological replicate 1 |
| GSM771026 |
Pancreas from adult WT mice, biological replicate 2 |
| GSM771027 |
Pancreas from adult WT mice, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA144813 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31150_RAW.tar |
18.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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