Ceramide inhibits pancreatic β-cell insulin production and mitogenesis and mimics the actions of interleukin-1β

AbstractCeramide, generated during sphingomyelinase-induced sphingolipid cleavage, is considered an important mediator in cytokine signaling. The effects of endogenously generated and exogenously delivered ceramide on long-term insulin secretion and replication by pancreatic β-cells were investigated, and compared to the effects of interleukin 1β (ILI-1β). Generation of β-cell ceramide by exogenous sphingomyelinase, or addition of cell-permeant ceramide analogs C2-ceramide and C6-ceramide, caused inhibitory effects on β-cell insulin production and mitogenesis mimicing those evoked by IL-1β. Hence, ceramide may be involved in transducing the cytostatic and cytotoxic actions of IL-1β in the β-cell