Fatty acids potentiate interleukin-1β toxicity in the β-cell line INS-1E

Evidence for "lipotoxicity," i.e., negative effects of fatty acids (FA) on pancreatic beta-cells is incomplete. Here, we tested whether non-toxic concentrations of FA potentiate toxic effects of interleukin-1beta (IL-1beta). Culture of INS-1E clonal beta-cells for 2-6 days with 70 muM docosahexaenoic acid (DHA), eicosapentaenoic acid, arachidonic acid, 0.1 mM linoleic acid, or 0.1-0.2 mM oleic acid exerted no or minor negative effects on cell viability (MTT assay). Viability was reduced by 0.5 ng/ml IL-1beta. All tested FA significantly aggravated this effect after 6 days of culture. 1L-1beta also exerted negative effects on cellular insulin content and DHA and oleic acid aggravated these effects. L-NAME, an inhibitor of constitutive nitric oxide (NO) synthase, reduced the negative effects of IL-1beta per se but did not abolish the potentiating effects of FA. Conclusion: FA potentiate toxic effects of IL-1beta on beta-cells by mechanisms that include NO-independent ones. (C) 2002 Elsevier Science (USA). All rights reserved.