Multitasking Metformin

The diabetes drug metformin doesn’t work the way researchers thought. That surprise might lead to new opportunities for the widely used medication in treating cancer. Metformin has been in use since the 1950s to treat type 2 diabetes by suppressing glucose production and increasing the body’s sensitivity to the effects of insulin. The drug was thought to work by switching on a kinase, which then activates a protein complex. That complex was believed to ultimately shut down another kinase known as mammalian target of rapamycin (mTOR), which plays a central role in regulating cell growth and metabolism. But the University of Cincinnati’s George Thomas and colleagues found otherwise. In cells from fruit flies and mice, they noticed that metformin blocks mTOR even when the upstream kinase and protein complex are absent (Cell Metab. 2010, 11, 390). Their work suggests metformin disables mTOR via GTP hydrolases instead. The researchers believe metformin could be an alternative to cancer drugs such as rapamycin, which also blocks mTOR but interferes with glucose control when used long-term.