| First Author | Taguchi Y | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 23 | Pages | 12029-38 |
| PubMed ID | 27059959 | Mgi Jnum | J:235035 |
| Mgi Id | MGI:5792642 | Doi | 10.1074/jbc.M116.728170 |
| Citation | Taguchi Y, et al. (2016) Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet beta-Cell Endoplasmic Reticulum Stress and Proliferation. J Biol Chem 291(23):12029-38 |
| abstractText | 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 (SPPases), 1 and 2, which are encoded by the Sgpp1 and Sgpp2 genes, respectively. SPPase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. SPPase 1 is important for skin homeostasis, but little is known about the functional role of SPPase 2. To identify the functions of SPPase 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 pancreatic islet size; however, they exhibited defective adaptive beta-cell proliferation that was demonstrated after treatment with either a high-fat diet or the beta-cell-specific toxin, streptozotocin. Importantly, beta-cells from untreated Sgpp2(-/-) mice showed significantly increased expression of proteins characteristic of the endoplasmic reticulum stress response compared with beta-cells from WT mice, indicating a basal islet defect. Our results show that Sgpp2 deletion causes beta-cell endoplasmic reticulum stress, which is a known cause of beta-cell dysfunction, and reveal a juncture in the sphingolipid recycling pathway that could impact the development of diabetes. |
