The most commonly prescribed diabetic medication for the Type 2 condition is ‘Metformin’—a drug with a mysterious mechanism of action but ultimately controls blood sugar levels. Now, a collaborative team of researchers have aimed to investigate metformin using computational analysis. Their findings, published in Cell Reports, shows that metformin involves key biochemical actviation in many cellular physiology that support an extension of a healthy lifespan.
“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.”
Computational analysis revealing targets of metformin. Caption and Image Credit: Salk Institute
Earlier studies on metformin revealed that the only biochemical mechanism activated by its action was the ‘AMPK pathway’ which stalls cell growth and alters metabolism when nutrients are low. However, these studies led scientists to believe that more pathways are activated by metformin beyond the AMPK.
“Being mentored by John Yates, one of the top mass spectrometry investigators in the world, and Reuben Shaw, an expert in the field of metabolism, enabled me to both develop and apply a novel technology to a critical biological question: What pathways are regulated by metformin in the liver?” says Ben Stein, first author and postdoctoral associate at Weill Cornell Medical College.
How scientists were able to tell what kind of pathways were specifically activated? For one, they developed a novel method to investigate proteins known as ‘kinases’ that transfer phosphate groups and are critical on/off switches in cells that can be rapidly flipped by the actions of metformin. These regulatory kinases are involved in aging which thus implicates metformin.
“The results broaden our understanding of how metformin induces a mild stress that triggers sensors to restore metabolic balance, explaining some of the benefits previously reported such as extended healthy aging in model organisms taking metformin. The big questions now are what targets of metformin can benefit the health of all individuals, not just type 2 diabetics,” says William R. Brody Chair.
Source: Science Daily