Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity.

ABSTRACT: Increasing evidence suggests a crucial role of inflammation in cytokine-mediated β-cell dysfunction and death in type 1 diabetes mellitus, although the mechanisms are incompletely understood. Sphingosine 1-phosphate (S1P) is a multifunctional bioactive sphingolipid involved in the development of many autoimmune and inflammatory diseases. Here, we investigated the role of intracellular S1P in insulin-secreting INS1E cells by genetically manipulating the S1P-metabolizing enzyme S1P lyase (SPL). The expression of spl was down-regulated by cytokines in INS1E cells and rat islets. Overexpression of SPL protected against cytokine toxicity. Interestingly, the SPL overexpression did not suppress the cytokine-induced NFκB-iNOS-NO pathway but attenuated calcium leakage from endoplasmic reticu

SUBMITTER: Hahn C 

PROVIDER: S-EPMC5724014 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature