Reduced mitochondrial Ca2+ accumulation and respiration in MKR islets. Islets from 3-week-old (A), 5-week-old (C), and 10-week-old (E) mice were loaded with Rhod-2 and photon emission monitored in a chamber perifused with Krebs-Ringer buffer containing basal
(1 mmol/l) and 11 mmol/l glucose. A, C, and E: Representative kinetic traces from a single islet are shown and families of traces from three to four islets per genotype
are shown in Fig. S5. B, D, and F: Summary of the difference in Rhod-2 fluorescence (relative fluorescent units [RFU]) between basal (1 mmol/l) and maximal
(11 mmol/l) glucose (n = 3–5 independent experiments, and each experiment contains nine islets from three mice per genotype). G and H: O2 consumption in 10-week-old islets supported by respiratory substrates for complex IV (ascorbate and TMPD) was measured. Addition
of ascorbate/TMPD (10 mmol/l/0.4 mmol/l) is marked by an arrow. G: Representative trace. H: The slopes of the oxygen consumption curves were measured between 5 and 10 min, the background ascorbate/TMPD effect in
the absence of islets was subtracted, and genotypes were compared. WT = solid black line; MKR = gray dotted line (n = 3 with 8–10 mice per genotype in each experiment). Data are means ± SE. **P < 0.01; ***P < 0.001 compared with age-matched WT.