Ceramide inhibits pancreatic beta-cell insulin production and mitogenesis and mimics the actions of interleukin-1 beta.
Ceramide, 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 beta-cells were investigated, and compared to the effects of interleukin 1 beta (IL-1 beta). Generation of beta-cell ceramide by exogenous sphingomyelinase, or addition of cell-permeant ceramide analogs C2-ceramide and C6-ceramide, caused inhibitor effects on beta-cell insulin production and mitogenesis mimicing those evoked by IL-1 beta. Hence, ceramide may be involved in transducing the cytostatic and cytotoxic actions of IL-1 beta in the beta-cell.
Sjöholm
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Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology*; D046508:Culture Techniques; D006131:Growth Inhibitors; D007328:Insulin / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology
D002518:Ceramides; D006131:Growth Inhibitors; D007328:Insulin; D007375:Interleukin-1; D013108:Sphingomyelin Phosphodiesterase