Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA2β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes.

Journal Article (Journal Article)

Type 1 diabetes (T1D) development, in part, is due to ER stress-induced β-cell apoptosis. Activation of the Ca2+-independent phospholipase A2 beta (iPLA2β) leads to the generation of pro-inflammatory eicosanoids, which contribute to β-cell death and T1D. ER stress induces iPLA2β-mediated generation of pro-apoptotic ceramides via neutral sphingomyelinase (NSMase). To gain a better understanding of the impact of iPLA2β on sphingolipids (SLs), we characterized their profile in β-cells undergoing ER stress. ESI/MS/MS analyses followed by ANOVA/Student's t-test were used to assess differences in sphingolipids molecular species in Vector (V) control and iPLA2β-overexpressing (OE) INS-1 and Akita (AK, spontaneous model of ER stress) and WT-littermate (AK-WT) β-cells. As expected, iPLA2β induction was greater in the OE and AK cells in comparison with V and WT cells. We report here that ER stress led to elevations in pro-apoptotic and decreases in pro-survival sphingolipids and that the inactivation of iPLA2β restores the sphingolipid species toward those that promote cell survival. In view of our recent finding that the SL profile in macrophages-the initiators of autoimmune responses leading to T1D-is not significantly altered during T1D development, we posit that the iPLA2β-mediated shift in the β-cell sphingolipid profile is an important contributor to β-cell death associated with T1D.

Full Text

Duke Authors

Cited Authors

  • Ali, T; Lei, X; Barbour, SE; Koizumi, A; Chalfant, CE; Ramanadham, S

Published Date

  • October 21, 2021

Published In

Volume / Issue

  • 26 / 21

PubMed ID

  • 34770770

Pubmed Central ID

  • PMC8587436

Electronic International Standard Serial Number (EISSN)

  • 1420-3049

Digital Object Identifier (DOI)

  • 10.3390/molecules26216361


  • eng

Conference Location

  • Switzerland