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School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
¹ School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland

(Correspondence should be addresses to P Newsholme; Email: philip.newsholme{at}ucd.ie)

We have investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines on ß-cell metabolism and insulin secretion using clonal BRIN-BD11 ß cells. Addition of IL-1ß, tumour necrosis factor- and IFN- (at concentrations that did not induce apoptosis) inhibited chronic (24 h) and acute stimulated levels of insulin release (by 59 and 93% respectively), increased cellular glucose and alanine consumption, and also elevated lactate and glutamate release. However, ATP levels and cellular triacylglycerol were decreased while glutathione was increased. We conclude that sub-lethal concentrations of pro-inflammatory cytokines appear to shift ß-cell metabolism away from a key role in energy generation and stimulus–secretion coupling and towards a catabolic state which may be related to cell defence.