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Mouse results unlock metformin's secrets

Preclinical research brings mechanism understanding a step closer, could lead to new drugs
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Proposed model of how metformin works--courtesy of Dr. Morris Birnbaum, Perelman School of Medicine, University of Pennsylvania; Nature

A new glimpse into the workings of the anti-diabetic drug metformin showing that its mechanism of action isn't quite what people have thought could lead to new drugs for the growing need in Type 2 diabetes.

Metformin, one of the biguanides, is the most frequently used drug in Type 2 diabetes. The first publications on the drug date back to 1922, but despite all of these years of use, its mechanism has never been quite clear.

In Type 2 diabetes, resistance to insulin means the hormone can't control the liver's output of glucose triggered by glucagon, leading to too much sugar in the blood. Metformin is able to cut this output, and previous theories suggested that it worked by activating an enzyme, but this theory was quashed in 2010.

A team from the U.S. and France, led by the Perelman School of Medicine at the University of Pennsylvania, found that metformin blocks glucagon-dependent glucose output from the liver in mice by indirectly blocking the action of one of the enzymes, adenylate cyclase. The research was published in Nature.

These findings could lead to new drugs that could avoid metformin's unfortunate gastrointestinal side effects and even help those patients who have become resistant to the drug.

- read the press release
- see the abstract

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