Doctors commonly prescribe metformin to help people with type 2 diabetes lower their blood sugar levels. The drug increases insulin sensitivity through its effects on glucose metabolism. However, although there is clear evidence of metformin effectiveness, scientists do not fully understand how it interacts with cells and tissues at the molecular level. Now, a new Cell Reports study has mapped metformin activity in the liver and yielded some surprising results. Using cell cultures and mice, the researchers identified numerous biochemical switches for turning various cell and molecular processes on and off. The findings shed light not only on metformin mechanism of glucose control, but also on a surprising number of other reactions and pathways. The researchers suggest, for instance, that the new findings could help explain recent revelations about metformin apparent ability to promote healthy aging. Doctors commonly prescribe metformin to help people with type 2 diabetes lower their blood sugar levels. The drug increases insulin sensitivity through its effects on glucose metabolism. Metformin may hold surprising benefits in the fight against age-related illness. However, although there is clear evidence of metformin effectiveness, scientists do not fully understand how it interacts with cells and tissues at the molecular level. Now, a new Cell Reports study has mapped metformin activity in the liver and yielded some surprising results. Using cell cultures and mice, the researchers identified numerous biochemical switches for turning various cell and molecular processes on and off. The findings shed light not only on metformin mechanism of glucose control, but also on a surprising number of other reactions and pathways. Large-scale clinical trials of metformin are already under way to test the drug's effectiveness in extending life span and health span that is, the proportion of a person life span that they spend in good health. However, the underlying biochemistry has been unclear. Teams from three research centers worked on the study: the Salk Institute for Biological Studies, the Scripps Research Institute both in La Jolla, CA and Weill Cornell Medical College in New York. These results, says Reuben J. Shaw, one of the study corresponding authors,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.These are pathways that neither we, nor anyone else, would have imagined,he adds. Shaw is a professor of molecular and cell biology at the Salk Institute and director of the Salk Cancer Center. The researchers also identified new targets and cell mechanisms that the AMPK pathway controls that may also be crucial to metformin success. The teams plan to continue studying the new signaling pathways to deepen their understanding of the many effects of metformin. They are keen to find out how all individuals, not just those with type 2 diabetes, might benefit from metformin and which targets might be involved.
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