The Energy Producing Mitochondria
Mitochondria are the energy produc- ing organelles found in virtually all hu- man cells. Mitochondria contain an outer membrane which allows small molecules to pass through selectively and an inner membrane, or matrix, where metabolic processes occur. DNA and enzymes can also be found in the inner matrix.
One of the main duties of mitochon- dria is to metabolize and breakdown carbo- hydrates and fatty acids in order to generate energy. Beta oxidation is a process in which fatty acids are broken down and metabo- lized into Acetyl-CoA. Acetyl-CoA is then utilized in the Krebs Cycle, which produces carbon dioxide, NADH and FADH2. These molecules are involved in the electron transport chain, or ETC, where oxidative phosphorylation occurs, leading to the formation of adenosine triphosphate, better known as ATP, the major energy source for most cellular processes.
The process of the ETC creates reac-
tive oxygen species, or ROS. ROS function as secondary messengers and can directly kill bacteria or cause pro-infl ammatory responses to signal other infl ammatory markers to attack viruses and bacteria. On
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the downside, they can also cause direct damage to a cell, inducing apoptosis, or cell death, via oxidative stress. Because of their complex involvement in many cellular processes, mitochondria dysfunction has been a widely researched topic as it per- tains to disease development and progres- sion. This is particularly true in the case of diabetes.
Any alteration in mitochondria func-
tion would negatively affect insulin secre- tion from beta cells of the pancreas. It is believed that the production of ROS from the mitochondria may interfere with insulin signaling in muscle cells, leading to insulin resistance, a defi ning feature of Type 2 diabetes. In healthy individuals, insulin is released from the pancreas in response to elevated glucose levels and helps to push glucose back into the cells. In individu- als with insulin resistance, cells are not responsive to the effects of insulin leading to elevated blood glucose levels. Lowered production of ATP would affect the ability of glucose to trigger insulin. Persons with diabetes typically produce more ROS, lead- ing to mitochondrial and cellular oxidative damage, thus leading to further worsening of diabetic complications.
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Biopsies of skeletal and cardiac muscle of persons suffering from Type 2 diabetes revealed mitochondria tend to be smaller in size than healthy individuals, further contributing to insulin sensitivity. Reduced metabolic process is also observed in mito- chondria of diabetic individuals, leading to less energy and DNA production overall.
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Antioxidants play an important role in the management and reduction of cellularly damaging oxidative species. Coenzyme Q10, is an antioxidant that is mobilized in the ETC. In its ubiquinone forms has been show to help reduce free radical damage and help support mitochondrial integrity. Other important antioxidants include Vitamin E, Vitamin C and glutathione and have been shown to improve mitochondrial function.
Putting It All Together While oxidative stress and infl amma-
tion are two serious sequelae of poorly- controlled diabetes, they are unfortunately not often included in the discussion around diabetic treatment approaches. Recent research clearly presents a strong argument for investigating the effects of the disease, and of its treatment, on the cellular level, as there is much more to be uncovered in the world of cellular endocrinology.
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