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.
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.
Authors: Eluzia C Peres-Emidio; Gustavo J C Freitas; Marliete C Costa; Ludmila Gouveia-Eufrasio; Lívia M V Silva; Anderson P N Santos; Paulo H F Carmo; Camila B Brito; Raquel D N Arifa; Rafael W Bastos; Noelly Q Ribeiro; Lorena V N Oliveira; Monique F Silva; Tatiane A Paixão; Alessandra M Saliba; Caio T Fagundes; Daniele G Souza; Daniel A Santos Journal: Front Cell Infect Microbiol Date: 2022-04-25 Impact factor: 6.073
Authors: Ismail Syed; Maria F Rubin de Celis; James F Mohan; Pedro M Moraes-Vieira; Archana Vijayakumar; Andrew T Nelson; Dionicio Siegel; Alan Saghatelian; Diane Mathis; Barbara B Kahn Journal: J Clin Invest Date: 2019-08-05 Impact factor: 14.808