Doctors usually prescribe metformin to help lower blood sugar levels for people with type 2 diabetes. The medicine increases the sensitivity of insulin by its effects on the metabolism of glucose.
Despite clear evidence of the effectiveness of metformin, however, researchers do not fully understand how it interacts at the molecular level with cells and tissues.
Now, a recent study of Cell Reports has mapped the activity of metformin in the liver and provided some surprising results.
The researchers identified several biochemical switches using cell cultures and mice to turn on and off different cell and molecular processes.
The results shed light not only on the glucose control mechanism of metformin, but also on an amazing number of other reactions and pathways.
For example, the researchers suggest that the new findings may help explain recent revelations about the apparent ability of metformin to promote healthy aging.
Metformin’s large-scale clinical trials are already underway to test the efficacy of the drug in improving the lifetime and span of health that is, the proportion of a person’s life span that they spend in good health. However, the underlying biochemistry has been unclear.
The study was conducted out by teams from three research centers: the Salk Institute for Biological Studies, the Scripps Research Institute in La Jolla, California, and the Weill Cornell Medical College in New York.
Reuben J. Shaw, one of the authors of the study, states, “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.” He added, “These are pathways that neither we, nor anyone else, would have imagined,”.
Shaw is a molecular and cell biology professor at the Salk Institute and the Salk Cancer Center’s director.
The new studies suggest that metformin’s benefits to healthy aging could be through its interaction with protein kinase D and MAPKAPK2.
In a statement Prof. Shaw said “We never imagined these two kinases would have anything to do with metformin,”
The researchers also identified new targets and cell pathways that are controlled by the AMPK pathway, which can also be crucial to the success of metformin.
To expand their understanding of the many effects of metformin, the teams plan to continue researching the new signaling pathways.
So they also are keen to find out how all people, not just those with type 2 diabetes, could benefit from metformin and which additional targets might be involved.
Prof. Reuben J. Shaw said: “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.”


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