Wang Y., An H., Liu T., Qin C., Sesaki H., Guo S., Radovick S., Hussain M., Maheshwari A., Wondisford F. E. , O'Rourke B., He L.
- Metformin is the first-line medication for the treatment of type 2 diabetes (T2D), particularly in people who are overweight. It is estimated that around 150 million people around the world.
- Metformin works mainly by improving patients' hyperglycemia (suppressing liver's glucose production) and alleviating insulin resistance. However, its mechanisms of actions are currently not understood.
- It is known that mitochondrial dysfunctions are involved in the development of T2D and that patients with T2D have decreased mitochondrial copy number and respiration.
- The author show that therapeutic doses of metformin increase mito respiration, ATP level and membrane potential and promote mitochondrial fission in liver cells. Through knock-out studies, they determine that the enzyme AMPK is required for metformin to be effective.
- The author also report that very high concentration of the drug can lead to a stop of respiration, by depleting cellular ADP levels. Respiration was restored through the addition of exogenous ADP.
