The widely used type 2 diabetes drug metformin may work in a different way than previously believed, according to new research published online in the journal Nature.
Metformin lowers blood glucose levels by decreasing the liver’s production of the blood sugar-regulating hormone insulin. But scientists have been unable to confirm exactly how it is able to do so.
It was previously thought that the drug reduces glucose synthesis by activating the enzyme AMP-activated protein kinase (AMPK). However, this theory was challenged in 2010 after genetic studies found that metformin still worked in mice without this enzyme.
In the latest study, an international team of scientists, led by Dr. Morris J. Birnbaum, a professor at the University of Pennsylvania’s Institute for Diabetes, Obesity, and Metabolism (IDOM), found “a novel mechanism” by which the frequently prescribed medicine antagonises the action of the hormone glucagon to lower fasting glucose levels.
“The team showed that metformin leads to the accumulation of AMP in mice, which inhibits an enzyme called adenylate cyclase, thereby reducing levels of cyclic AMP and protein kinase activity, eventually blocking glucagon-dependent glucose output from liver cells,” they explained.
The researchers said the new findings could lead to the development of a new drug that mimics the way in which adenylate cyclase is inhibited by metformin, adding that such a treatment could eliminate the adverse effects associated with metformin and may even work for patients who are resistant to the medicine .

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