Role of Uncoupling Proteins and the mitochondrial KATP channel in mitochondrial dysfunction in the setting of Diabetes

Type two diabetes (T2D) is characterized by the body’s inability to respond to insulin leading to insulin resistance. Studies show that this leads to mitochondrial dysfunction in T2D. A recent study suggested that damage to the mitochondrial K_ATP channel occurs in diabetic human myocardium, which leads to the inability of the mitochondria to synthesize enough ATP to meet the energetic demands. Mitochondria uncoupling proteins (UCP) have been identified as factors that increase myocardial O₂ consumption without increasing ATP synthesis, thus decreasing cardiac efficiency in diabetic hearts. The interaction between these two entities in mediating mitochondrial dysfunction in patients with T2D is unknown. The main objective of this project is to determine if the mitochondrial K_ATP channel and UCP work together to alter mitochondrial structure and function in T2D. Epicatechin (EPI), flavanol found in cocoa, is described to be cardio protective by inhibiting mitochondrial dysfunction. We tested to see if it decreases the progression towards heart complications associated with diabetes. Our preliminary results demonstrated that animals on a high energy diet consisting of 10% lard and 10% glucose in addition to their basal diet had changes in body weight (~44%) compared to sham animals (~37%),while EPI treatment had ~33% in both. Moreover, EPI treated diabetic rats decreased blood glucose levels (351.2 mg/dL) when compared to control diabetic rats (519 mg/dL). More work will be done on the role of EPI in inhibiting mitochondrial dysfunction , as well as the mechanical and chemical signaling occurring between the mitochondrial K_ATP channel and UCPs.