FIG. 7.

Pathophysiological effects of MAO-derived byproducts within myocardium from patients with type 2 diabetes. MAO expression and activity are increased in the myocardium of patients with type 2 diabetes, suggesting increased flux of catecholamines through MAO. In the myocardium, MAO-derived byproducts form catechol-modified protein adducts (post-translational modifications) on enzymes responsible for fatty acid oxidation, tricarboxylic acid cycle, and OxPHOS (energy disruption). In patients with diabetes, the compromised ALDH2 activity would exacerbate these toxicities by creating a “detoxification bottleneck.” Chronic carbonyl stress due to hyperglycemia and insulin resistance may contribute to hypertrophy, fibrosis, and EP derangements, ultimately leading to electromechanical dysfunction in the myocardium of patients with diabetes. ANT, adenine nucleotide translocase; EP, electrophysiology; IMM, inner-mitochondrial membrane; OCT3/ENMT, organic cation transporter-3/extraneuronal monoamine transporter; OMM, outer mitochondrial membrane.