期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 392, 期 2, 页码 207-211出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.01.016
关键词
Blood glucose; Diabetes; Insulin; S1P(2)-deficient mice; S1P(2)-specific antagonist
资金
- National Hospitals of Japan
- Takeda Science Foundation
- National Institutes of Health [DA019674, NS048478]
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 W-F 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. (C) 2010 Elsevier Inc. All rights reserved.
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