(A) Levels of intramyocellular lipid (IMCL) triglycerides in atrial tissue homogenate prepared from type 2 diabetic and nondiabetic patients. (B) Plot showing correlation between myocardial triglycerides and HbA_1c in nondiabetic (open circles) and diabetic (closed circles) patients. (C) A representative trace of adenine diphosphate (ADP)-stimulated O₂ consumption in permeabilized human atrial myofibers in response to incrementally increasing concentrations of palmitoyl-L-carnitine (PC). Permeabilized fibers in the absence of substrate (deFB) were added to respiratory medium in the presence of 3 mM ADP, 5 mM glucose, and 1 U/ml hexokinase (to create permanent, maximally phosphorylating respiratory state), followed by incrementally increasing concentrations of PC in the presence of 2 mM malate. The blue line is the O₂ concentration in the medium (left y-axis); the red line is the rate of O₂ consumption (right y-axis). (D) Kinetic plots of palmitoyl-L-carnitine–supported respiration (i.e., fatty acid oxidation) in permeabilized atrial myofibers prepared from both groups of patients, and the correlation of maximal oxidation rate (V_max) with glycosylated hemoglobin (HbA_1c) (E). Quantified data are mean ± SEM, n = 9 to 12 patients in each group. *p < 0.05 versus nondiabetic patients.

(A) Kinetic plots of ADP-stimulated respiration supported by 10 mM pyruvate and 2 mM malate in permeabilized atrial myofibers prepared from diabetic and nondiabetic patients. (B) Minimal (S₀) and maximal (S_ADP) respiration supported by succinate in both groups. (C) Representative trace of a typical O₂ consumption experiment in permeabilized human atrial myofibers using sequential addition of oxidative substrates, nucleotides, and inhibitors to assess contribution of multiple oxidative substrates to total respiratory flux. Permeabilized fibers in the absence of substrate were added to respiratory medium (deFB), followed by 5 mM glutamate/2 mM malate (GM₀), 5 mM ADP (GM_ADP), 10 mM succinate (GMS_ADP), 20 µM cytochrome C (to test for intactness of outer mitochondrial membrane), 10 µg/ml oligomycin (GMS_O), and 3 µM carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (GMS_F). (D) Quantified rates of glutamate-supported respiration in permeabilized atrial myofibers of diabetic and nondiabetic patients. Quantified data are mean ± SEM, n = 7 to 8 patients in each group. *p < 0.05 versus nondiabetic patients. Abbreviations as in Figure 1.

(A) Kinetic plots of mitochondrial H₂O₂ emission and (B) O₂ consumption in permeabilized atrial myofibers prepared from diabetic and nondiabetic patients supported by incrementally increasing concentrations of succinate in the presence of 10 µg/ml of oligomycin (to inhibit adenosine triphosphatase and ensure basal respiratory state) + 5 mM glutamate, 2 mM malate. (C) Quantified rates of mitochondrial hydrogen peroxide (H₂O₂) emission during respiration in the presence of 125 µM ADP, 5 mM glucose, 1 U/ml hexokinase (to create permanent, submaximally phosphorylating respiratory state), supported by 75 µM palmitoyl-L-carnitine + 2 mM malate (PCM), 5 mM glutamate (PCMG), and 10 mM succinate (PCMGS). (D) Ratio of moles of H₂O₂ emitted per mole of O₂ consumed during respiration supported by palmitoyl-L-carnitine. Quantified data are mean ± SEM, n = 7 to 9 patients in each group. *p < 0.05 versus nondiabetic patients. Abbreviations as in Figure 1.

(A) Quantified levels of oxidized glutathione (GSSG) and total glutathione (GSH_t) in atrial tissue of diabetic and nondiabetic patients. (B) Redox environment of atrial tissue as determined by GSH/GSSG ratio. (C) Representative immunoblot and (D) densitometric quantification of hydroxynonenal (HNE)-modified proteins in atrial tissue from both groups of patients. (E) Representative immunoblot and (F) densitometric quantification of 3-nitrotyrosine–modified proteins in atrial tissue from both groups of patients. Quantified data are mean ± SEM, n = 8 to 11 patients in each group. *p < 0.05 versus nondiabetic patients.