Roles of ceramide and sphingolipids in pancreatic beta-cell function and dysfunction

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Author
Boslem, E; Meikle, PJ; Biden, TJDate
2012-05-01Source Title
IsletsPublisher
TAYLOR & FRANCIS INCUniversity of Melbourne Author/s
Meikle, PeterAffiliation
Bio21Metadata
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Journal ArticleCitations
Boslem, E., Meikle, P. J. & Biden, T. J. (2012). Roles of ceramide and sphingolipids in pancreatic beta-cell function and dysfunction. ISLETS, 4 (3), pp.177-187. https://doi.org/10.4161/isl.20102.Access Status
Open AccessAbstract
Recent technical advances have re-invigorated the study of sphingolipid metabolism in general, and helped to highlight the varied and important roles that sphingolipids play in pancreatic β-cells. Sphingolipid metabolites such as ceramide, glycosphingolipids, sphingosine 1-phosphate and gangliosides modulate many β-cell signaling pathways and processes implicated in β-cell diabetic disease such as apoptosis, β-cell cytokine secretion, ER-to-golgi vesicular trafficking, islet autoimmunity and insulin gene expression. They are particularly relevant to lipotoxicity. Moreover, the de novo synthesis of sphingolipids occurs on many subcellular membranes, in parallel to secretory vesicle formation, traffic and granule maturation events. Indeed, the composition of the plasma membrane, determined by the activity of neutral sphingomyelinases, affects β-cell excitability and potentially insulin exocytosis while another glycosphingolipid, sulfatide, determines the stability of insulin crystals in granules. Most importantly, sphingolipid metabolism on internal membranes is also strongly implicated in regulating β-cell apoptosis.
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