Metformin is the most commonly prescribed Type 2 diabetes drug, yet scientists still do not fully know how it works to control blood sugar levels.
In a collaborative effort, researchers from the Salk Institute, The Scripps Research Institute, and Weill Cornell Medical College have used novel technology to investigate why it functions so well.
The findings, which identified a surprising number of biochemical “switches” for various cellular processes, could also explain why metformin has been shown to extend healthspan and life span in recent studies.
“These results provide us with new avenues to explore in order to understand how metformin works as a diabetes drug, along with its health-span-extending effects,” says professor Reuben Shaw, co-corresponding author of the paper and the director of Salk’s NCI-designated Cancer Center. “These are pathways that neither we nor anyone else, would have imagined.”
Previously, the only biochemical pathway that was known to be activated by metformin was the AMPK pathway, which Shaw discovered stalls cell growth and changes metabolism when nutrients are scarce, as can occur in cancer. But the scientists believed more pathways than AMPK might be involved.
The scientists developed a novel screening platform to examine kinases, the proteins that transfer phosphate groups, which are critical on/off switches in cells and can be rapidly flipped by metformin.
Using this technology, the researchers were able to decode hundreds of regulatory “switch-flipping” events that could affect healthy aging.
The study was published in Cell Reports.
- Salk Institute. (2019, December 4). Diabetes drug has unexpected, broad implications for healthy aging: Scientists discover multiple mechanisms at work in widely-used diabetes drug metformin. ScienceDaily. Retrieved December 11, 2019 from www.sciencedaily.com/releases/2019/12/191204090815.htm