| First Author | Imasawa T | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 392 |
| Issue | 2 | Pages | 207-11 |
| PubMed ID | 20060809 | Mgi Jnum | J:157866 |
| Mgi Id | MGI:4437181 | Doi | 10.1016/j.bbrc.2010.01.016 |
| Citation | Imasawa T, et al. (2010) Blockade of sphingosine 1-phosphate receptor 2 signaling attenuates streptozotocin-induced apoptosis of pancreatic beta-cells. Biochem Biophys Res Commun 392(2):207-11 |
| abstractText | Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that acts through five cognate G protein-coupled receptors (S1P(1)-S1P(5)) and regulates many critical biological processes. Recent studies indicated that S1P at nanomolar concentrations significantly reduces cytokine-induced apoptosis of pancreatic beta-cells in which genes for S1P(1)-S1P(4) are co-expressed. However, the S1P receptor subtype(s) involved in this effect remains to be clarified. In this study, we investigated the potential role of S1P(2) in streptozotocin (STZ)-induced apoptosis of pancreatic beta-cells and progression of diabetes. S1P(2)-deficient (S1P(2)(-/-)) mice displayed a greater survive ability, lower blood glucose levels, and smaller numbers of TUNEL-positive apoptotic beta-cells to administration of a high dose of STZ than wild-type (WT) mice. S1P(2)(-/-) mice showed higher insulin/glucose ratios (an index of relative insulin deficiency) and larger insulin-positive islet areas to administration of a low dose of STZ than WT mice. Moreover, administration of JTE-013, a S1P(2)-specific antagonist, to WT mice ameliorated STZ-induced blood glucose elevation and reduced the incidence of diabetes. Our findings indicate that blockade of S1P(2) signaling attenuates STZ-induced apoptosis of pancreatic beta-cells and decreases the incidence of diabetes. |
