GLP-1 decreases mitochondrial potential and engages its cognate receptor to increase [ATP/ADP]cyto. A, Elevated glucose (17 mM; G17) stimulates rapid and large excursions in TMRE fluorescence, indicating mitochondrial hyperpolarisation (representative trace from n = 6 recordings from four animals). B, GLP-1 under elevated glucose concentration slowly and subtly increases TMRE fluorescence, indicating minor hyperpolarizing effects on mitochondrial potential (representative trace from n = 6 recordings from four animals). C, As for B but in the presence of 3 mM glucose (representative trace from n = 7 recordings from four animals). D, TMRE responses to GLP-1 are significantly lower than those to glucose (**, P < .01 vs G17-alone, one-way ANOVA followed by Bonferonni's post hoc test). E, Representative Perceval trace showing reversible blockade of GLP-1 effects by 100 nM exendin 9-39 (Ex 9-39) (gray, raw; red, smoothed). F, Ex 9-39 abolishes GLP-1-induced [ATP/ADP]cyto dynamics and rises (*, P < .05 vs GLP-1 + Ex 9-39, Student paired t test, n = 11 recordings). G, Forced elevations in cAMP using forskolin (FSK) lead to increases in [ATP/ADP]cyto. H, FSK evoked ATP rises in all experiments performed (13/13). Unless otherwise stated, experiments are from islets taken from ≥ three animals.