RESUMO
It is believed that free fatty acids contribute to the pathogenesis of type 2 diabetes in humans. We have recently shown that lipoapoptosis of human beta-cells is specifically induced by saturated fatty acids while unsaturated had no effect. In the present study we tested the effect of co-incubation of different saturated and unsaturated free fatty acids on lipoapoptosis in beta-cells. RIN1046-38 cells and isolated human beta-cells were incubated with combinations of saturated fatty acids (palmitate, stearate) and mono- or polyunsaturated fatty acids (palmitoleate, oleate, and linoleate). Cells were incubated for 24-72 h with 1mM fatty acids. All unsaturated fatty acids tested completely prevented palmitate- or stearate-induced apoptosis of rat and human beta-cells as assessed by flow cytometric cell cycle analysis and TUNEL assay. This might suggest that apoptosis in vivo is predominantly determined by the content of unsaturated fatty acids in a mixed fatty acid pool.
Assuntos
Apoptose , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos/farmacologia , Ilhotas Pancreáticas/citologia , Células Cultivadas , Ácidos Graxos/antagonistas & inibidores , Ácidos Graxos/fisiologia , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/fisiologia , Humanos , Ilhotas Pancreáticas/efeitos dos fármacos , Ácidos Linoleicos/farmacologia , Ácidos Oleicos/farmacologia , Ácidos Palmíticos/farmacologia , Ácidos Esteáricos/antagonistas & inibidores , Células Tumorais CultivadasRESUMO
Plants are able to respond to herbivore damage with de novo biosynthesis of an herbivore-characteristic blend of volatiles. The signal transduction initiating volatile biosynthesis may involve the activation of the octadecanoid pathway, as exemplified by the transient increase of endogenous jasmonic acid (JA) in leaves of lima bean (Phaseolus lunatus) after treatment with the macromolecular elicitor cellulysin. Within this pathway lima bean possesses at least two different biologically active signals that trigger different biosynthetic activities. Early intermediates of the pathway, especially 12-oxo-phytodienoic acid (PDA), are able to induce the biosynthesis of the diterpenoid-derived 4,8, 12-trimethyltrideca-1,3,7,11-tetraene. High concentrations of PDA result in more complex patterns of additional volatiles. JA, the last compound in the sequence, lacks the ability to induce diterpenoid-derived compounds, but is highly effective at triggering the biosynthesis of other volatiles. The phytotoxin coronatine and amino acid conjugates of linolenic acid (e.g. linolenoyl-L-glutamine) mimic the action of PDA, but coronatine does not increase the level of endogenous JA. The structural analog of coronatine, the isoleucine conjugate of 1-oxo-indanoyl-4-carboxylic acid, effectively mimics the action of JA, but does not increase the level of endogenous JA. The differential induction of volatiles resembles previous findings on signal transduction in mechanically stimulated tendrils of Bryonia dioica.