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Advances in health and medicine.
Marjorie Bekaert Thomas
Advances in health and medicine.
Diabetes Channel
Reported January 8, 2013

New Discovery in Popular Diabetic Drug


(Ivanhoe Newswire) – For 50 years, type 2 diabetes patients have been relying on a drug that includes metformin, biguanides, to reduce overactive glucose production.  Now researchers have found that metformin works in a different way than previously understood!
Biguanides is the most prescribed drug to type 2 diabetics.  A major factor for diabetics is the inability of insulin to keep liver glucose output in check.
Researchers have found that metformin suppresses the liver hormone glucagon’s ability to generate an important signaling molecule, resulting in possible new drug targets.
"Overall, metformin lowers blood glucose by decreasing liver production of glucose. But we didn't really know how the drug accomplished that," Morris J. Birnbaum, MD, PhD, senior author and professor of the Willard and Rhoda Ware of Medicine at the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, was quoted as saying. 
About a decade ago, researchers believed that metformin reduced glucose synthesis by activating the enzyme AMPK.  In 2010, this theory was challenged by researchers in Paris, who found that the livers of mice without AMPK still responded to metformin, showing that blood glucose levels were being controlled outside of the AMPK pathway.  
When there is no food intake and glucose decreases, glucagon is secreted from the pancreas to signal that the liver should produce glucose.  
The study describes a mechanism by which metformin antagonizes the action of glucagon.  Researchers found that metformin leads to the accumulation of AMP in mice, which inhibits the enzyme called adenylate cyclase, and reduces levels of cyclic AMP and protein kinase activity.  
Researchers believe that adenylate cyclase could be a new drug target, mimicking the way it is inhibited by metformin.  This new strategy could avoid adverse side effects experienced by people who take metformin.  
SOURCE:  Nature, January 2013


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