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Role of the sphingolipid biostat in pancreatic βcell apoptosis induced by gluco‐lipotoxicity
Author(s) -
COANT Nicolas,
Veret Julien,
Giussani Paola,
Portha Bernard,
Berdyshev Evgeny V,
Le Stunff Herve
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.1
Subject(s) - lipotoxicity , sphingolipid , ceramide , apoptosis , sphingosine , medicine , endocrinology , microbiology and biotechnology , biology , chemistry , biochemistry , insulin , insulin resistance , receptor
Accumulated evidence suggests that Type 2 diabetes is often associated with abnormalities in lipids metabolism. Adverse effects of fatty acids on β cell function and viability are potentiated by the presence of hyperglycemia; this phenomenon is called gluco‐lipotoxicity. Sphingoid base‐1‐phosphates and ceramides are potent bioactive lipids involved in different patho‐physiological processes. This study was undertaken to determine whether these lipids are produced in palmitate‐treated pancreatic β cells and what role they play in palmitate‐induced beta cell apoptosis. Our lipidomic analysis revealed that palmitate at low and high glucose supplementation increased (dihydro)‐sphingosine‐1‐phosphate (S1P) and (dihydro)‐ceramides levels in INS‐1 β cells. This increase is associated with an increase of SphK1 and Cers4 proteins. Interestingly, we show that the over‐expression of Cers4 or the inhibition of SphK1 induces an increase of apoptosis induced by palmitate with 30 mM glucose, whereas down‐regulation of CerS4 by siRNA or over‐expression of SphK1 reduced apoptosis. Taken together, our results suggest an important role of the balance between S1P and ceramide (i.e. sphingolipid biostat) in β cell death induced by gluco‐lipotoxicity. These data suggest that targeting specific sphingolipid metabolites could be a novel therapeutic strategy to reduce the development of TD2.