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| Status |
Public on Jul 25, 2016 |
| Title |
Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-cell Endoplasmic Reticulum Stress and Proliferation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates basic cell functions through metabolic and signaling pathways. Intracellular metabolism of S1P is controlled, in part, by two homologous S1P phosphatases, 1 and 2, which are encoded by Sgpp1 and Sgpp2, respectively. S1P phosphatase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. S1P phosphatase 1 is important for skin homeostasis, but little is known about the functional role of S1P phosphatase 2. To identify the functions of S1P phosphatase 2 in vivo, we studied mice with the Sgpp2 gene deleted. In contrast to Sgpp1-/- mice, Sgpp2-/- mice had normal skin and were viable into adulthood. Unexpectedly, WT mice expressed Sgpp2 mRNA at high levels in pancreatic islets when compared with other tissues. Sgpp2-/- mice had normal blood insulin levels and pancreatic islet size; however, Sgpp2-/- mice treated with a high-fat diet (HFD) had significantly lower blood insulin levels and smaller pancreatic islets compared with WT mice. The smaller islets in the HFD-treated Sgpp2-/- mice had a significantly lower adaptive β-cell proliferation rate in response to the diet compared with HFD-treated WT mice. Importantly, β-cells from Sgpp2-/- mice fed a normal diet showed significantly increased expression of proteins characteristic of the endoplasmic reticulum (ER) stress response compared with β-cells from WT mice. Our results suggest that Sgpp2 deletion causes β-cell ER stress, which is a known cause of β-cell dysfunction, and reveal a novel juncture in the sphingolipid recycling pathway that could impact the development of diabetes.
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| Overall design |
Three replications of Mouse (WT vs KO) that were treated with with Normal and HFD foods.
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| Contributor(s) |
Taguchi Y, Allende ML, Mizukami H, Cook EK, Gavrilova O, Tuymetova G, Clarke BA, Chen W, Olivera A, Proia RL |
| Citation(s) |
27059959 |
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| Submission date |
Sep 17, 2015 |
| Last update date |
Feb 11, 2019 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
weipingChen@niddk.nih.gov
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| Phone |
301-496-0175
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| Organization name |
NIDDK/NIH
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| Department |
GCL
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| Lab |
Genomics Core Lab
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| Street address |
Bldg 8, Room 1A11, NIDDK/NIH
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA296080 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73131_RAW.tar |
76.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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