Fig 1. Cytokine-induced GSIS impairment and oxidative phosphorylation defects.

Cells were grown in fully supplemented RPMI (black bars) or exposed for 24 h to a combination of 2 ng/mL IL-1β plus 50 ng/mL IFN-γ (grey bars). The rate of insulin secretion was normalized to cell number (A) and was measured at 2.5 mM glucose (G2.5), 20 mM glucose (G20), 5 mM sodium pyruvate (PYR) or 30 mM KCl. Absolute mitochondrial respiration normalized to cell number was measured ± 20 mM glucose (B)—grey and black bars, respectively. Glucose-stimulated respiration used to make ATP or associated with proton leak was determined as oligomycin-sensitive or oligomycin-resistant mitochondrial oxygen uptake, respectively (C)—black and grey bars, respectively. Coupling efficiency of oxidative phosphorylation was calculated as the percentage of glucose-stimulated oxygen uptake used to make ATP (D). Data are means ± SEM from 3–7 individual experiments (S1 Data) with each condition repeated 3–5 times. Statistical significance of mean differences was tested by 2-way ANOVA: asterisks indicate statistically significant differences from equivalent RPMI controls (*P < 0.05 and ***P < 0.001). ^{a, ab} differs from the low-glucose condition (P < 0.05 and P < 0.001, respectively).