High fructose consumption leads to decreased glucose-stimulated insulin secretion and impaired mitochondrial response. A: glucose-stimulated insulin secretion in freshly isolated islets; n = 6–7 replicates of islet batches from ≥4 mice in each group. B: insulin secretion simulated with 10 mM leucine and 10 mM glutamine under nonstimulatory (2.8 mM) glucose conditions; n = 7 replicates of islet batches from 3 mice in each group. C: oxygen consumption rates in the basal (b) state, after glucose stimulation (+20 mM glc), after addition of the mitochondrial uncoupler FCCP (F), and after addition of the electron transport chain inhibitors oligomycin (O) and rotenone/antimycin (R/A). D: mitochondrial bioenergetics parameters were calculated based on measurements from those in C. Results are expressed as means ± SE; n = 4–7/group. **P < 0.01, ***P < 0.001, and ****P < 0.0001 by Student’s t-test.