Fatty acids potentiate interleukin-1beta toxicity in the beta-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 microM docosahexaenoic acid (DHA), eicosapentaenoic acid, arachidonic acid, 0.1mM linoleic acid, or 0.1-0.2mM 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. IL-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.


CONCLUSIONS
FA potentiate toxic effects of IL-1beta on beta-cells by mechanisms that include NO-independent ones.
Aarnes
M
M
Department of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway.
Schønberg
S
S
Grill
V
V
D002999:Clone Cells; D004357:Drug Synergism; D005227:Fatty Acids / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007375:Interleukin-1 / Q000633:toxicity*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology
D005227:Fatty Acids; D007328:Insulin; D007375:Interleukin-1; D019331:NG-Nitroarginine Methyl Ester