We have investigated the effects of prolonged exposure (24 hr) to pro-inflammatory cytokines on β cell metabolism and insulin secretion using clonal BRIN-BD11 beta cells. Expression of genes related to nutrient metabolism in the pancreatic beta-cell have been reported to be significantly altered in the presence of pro-inflammatory cytokines. We now report that addition of IL-1β, TNFα and IFNγ (at concentrations that did not result in a significant increase in cell death – IL-1β 0.3125U/ml, TNFα 31.25U/ml, IFNγ 15.625U/ml) inhibited chronic (24hr) and acute (20 min) levels of insulin release (2-fold and 5-fold), increased glucose and alanine consumption (2-fold and 2.5-fold) and also elevated lactate and glutamate release (3.7-fold and 1.5-fold). However, cellular triacylglycerol and ATP levels were decreased (2-fold and 1.2-fold) while glutathione was increased (1.5-fold). Pro-inflammatory cytokines appear to shift β-cell metabolism away from the primary role of stimulus-secretion coupling and towards a catabolic state which may be related to cell defence. This work is of importance to determining the beta cell response to inflammation, which is normally associated with the pathogenesis of type-1 diabetes.