We have investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines on beta-cell metabolism and insulin secretion using clonal BRIN-BD11 beta cells. Addition of IL-1beta, tumour necrosis factor-alpha and IFN-gamma (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 beta-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.