Context: 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.
Setting: 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.