IL-1beta-induced iNOS expression, NO release and loss in metabolic cell viability are resistant to inhibitors of ceramide synthase and sphingomyelinase in INS 832/13 cells.
BACKGROUND
Emerging evidence indicates regulatory roles for ceramide in the metabolic dysfunction of the islet beta cell. Recently, potential similarities between IL-1beta and ceramide on their effects on islet beta cell have been reported, including reduction in mitochondrial membrane potential and loss in metabolic cell viability.


OBJECTIVE
Herein, we investigated whether IL-1beta-induced nitric oxide synthetase (iNOS) expression, nitric oxide (NO) release and loss in metabolic cell viability require ceramide biosynthesis either via the activation of sphingomyelinase or ceramide synthase.


METHODS
Insulin-secreting INS 832/13 cells.


RESULTS
We found that two structurally-distinct inhibitors of sphingomyelinase activation (e.g., 3-O-methylsphingomyelin or desipramine) or ceramide biosynthesis inhibitor (e.g., fumonisin) failed to exert clear effects on IL-1beta-induced iNOS expression, NO release and loss in cell viability.


CONCLUSIONS
Taken together, our findings indicate that neither the sphingomyelinase nor the ceramide synthase activation is required for IL-1beta-induced metabolic abnormalities in insulin-secreting INS 832/13 cells.
Veluthakal
Rajakrishnan
R
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Jangati
Giridhar Rao
GR
Kowluru
Anjaneyulu
A
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004351:Drug Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*
D053583:Interleukin-1beta; D009569:Nitric Oxide; D010088:Oxidoreductases; D052247:Nitric Oxide Synthase Type II; C108138:dihydroceramide desaturase; D013108:Sphingomyelin Phosphodiesterase