Blockade of sphingosine 1-phosphate receptor 2 signaling attenuates streptozotocin-induced apoptosis of pancreatic β-cells

Toshiyuki Imasawa, Kentaro Koike, Isao Ishii, Jerold Chun, Yutaka Yatomi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that acts through five cognate G protein-coupled receptors (S1P1-S1P5) and regulates many critical biological processes. Recent studies indicated that S1P at nanomolar concentrations significantly reduces cytokine-induced apoptosis of pancreatic β-cells in which genes for S1P1-S1P4 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 S1P2 in streptozotocin (STZ)-induced apoptosis of pancreatic β-cells and progression of diabetes. S1P2-deficient (S1P2-/-) mice displayed a greater survive ability, lower blood glucose levels, and smaller numbers of TUNEL-positive apoptotic β-cells to administration of a high dose of STZ than wild-type (WT) mice. S1P2-/- 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 S1P2-specific antagonist, to WT mice ameliorated STZ-induced blood glucose elevation and reduced the incidence of diabetes. Our findings indicate that blockade of S1P2 signaling attenuates STZ-induced apoptosis of pancreatic β-cells and decreases the incidence of diabetes.

Original languageEnglish
Pages (from-to)207-211
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume392
Issue number2
DOIs
Publication statusPublished - 2010 Feb 5

Keywords

  • Blood glucose
  • Diabetes
  • Insulin
  • S1P-deficient mice
  • S1P-specific antagonist

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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