title: Differential protective effects of palmitoleic acid and cAMP on caspase activation and cell viability in pancreatic beta-cells exposed to palmitate.
abstract: Saturated and mono-unsaturated fatty acids exert differential effects on pancreatic beta-cell viability during chronic exposure. Long chain saturated molecules (e.g. palmitate) are cytotoxic to beta-cells and this is associated with caspase activation and induction of apoptosis. By contrast, mono-unsaturated fatty acids (e.g. palmitoleate) are not toxic and can protect against the detrimental effects of palmitate. In the present study, we show that the protective actions of palmitoleate in BRIN-BD11 beta-cells result in attenuated caspase activation following exposure to palmitate and that a similar response occurs in cells having elevated levels of cAMP. However, unlike palmitoleate, elevation of cAMP was unable to prevent the cytotoxic actions of palmitate since it caused a diversion of the pathway of cell death from apoptosis to necrosis. Palmitoleate did not alter cAMP levels in BRIN-BD11 cells and the results suggest that a change in cAMP is not involved in mediating the protective effects of this fatty acid. Moreover, they reveal that attenuated caspase activation does not always correlate with altered cell viability in cultured beta-cells and suggest that mono-unsaturated fatty acids control cell viability by regulating a different step in the apoptotic pathway from that influenced by cAMP.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Devon, Research Way, Plymouth, PL6 8BU, UK.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Welters
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Diakogiannaki
authors.forename: J Mark
authors.initials: JM
authors.lastname: Mordue
authors.forename: Moh
authors.initials: M
authors.lastname: Tadayyon
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019308:Palmitic Acid / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D005229:Fatty Acids, Monounsaturated; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D005576:Colforsin; C008757:palmitoleic acid; D019308:Palmitic Acid; D000242:Cyclic AMP; D020169:Caspases; D015056:1-Methyl-3-isobutylxanthine