The Sound of Evolution
Metformin
Mechanism of action:
Metformin is a biguanide derivative. After entering hepatocytes, metformin inhibits the activity of mitochondrial complex I, reducing ATP production and increasing the AMP/ATP ratio, which subsequently activates AMP-activated protein kinase. Once activated, AMP-activated protein kinase suppresses the expression of genes involved in gluconeogenesis, thereby decreasing hepatic glucose output. Metformin can also promote the expression and translocation of glucose transporter type 4 (GLUT4) in skeletal muscle and adipose tissue, increasing the efficiency of glucose uptake into cells and reducing insulin resistance.
Reference(s):
1. Witters LA et al. (2001). The blooming of the French lilac. J Clin Invest.
2. Ungar G et al. (1957). Pharmacological studies of a new oral hypoglycemic drug. Proc Soc Exp Biol Med.
3. Lord JM et al. (2003). Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ.