Fig. 4: Single treatment with empagliflozin increases mitochondrial ATP levels in the heart of T2D model mice.

a Schematic illustration of the treatment regimen (EMPA empagliflozin). b, c Representative fluorescence images of a live heart from each condition (EMPA empagliflozin) with or without increased ATP. Warmer colors indicate higher ATP concentrations. Scale bar: 2 mm. d FRET/GFP ratio indicating the amount of ATP in the heart under each condition (db/db [control]: n = 6, db/db [EMPA]: n = 8). *p = 0.013. e, f Representative images of mitochondrial ATP concentrations before (e) and 1 h after (f) empagliflozin 1000 nM administration. Scale bar: 25 μm. g Graph of the FRET/GFP ratio in mature cardiomyocytes with control (n = 22), empagliflozin 10 nM (n = 16), empagliflozin 100 nM (n = 14), empagliflozin 500 nM (n = 21) and empagliflozin 1000 nM (n = 27) (*p = 0.0010, 0.0058, 0.0000, 0.0000, respectively). h Biodistribution of empagliflozin in mitochondria in various tissues at 3 h after empagliflozin administration (n = 10). Heart: 0.56 ± 0.029, kidney: 3.95 ± 0.581, liver: 3.85 ± 0.216, small intestine: 1.15 ± 0.315, brain: 0.0 ± 0.000 nmol/mg.