Navigation Links
Most-used diabetes drug works in different way than previously thought
Date:1/6/2013

PHILADELPHIA - A team, led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, found that the diabetes drug metformin works in a different way than previously understood. Their research in mice found that metformin suppresses the liver hormone glucagon's ability to generate an important signaling molecule, pointing to new drug targets. The findings were published online this week in Nature.

For fifty years, one of the few classes of therapeutics effective in reducing the overactive glucose production associated with diabetes has been the biguanides, which includes metformin, the most frequently prescribed drug for type 2 diabetes. The inability of insulin to keep liver glucose output in check is a major factor in the high blood sugar of type 2 diabetes and other diseases of insulin resistance.

"Overall, metformin lowers blood glucose by decreasing liver production of glucose," says Birnbaum. "But we didn't really know how the drug accomplished that."

Imperfectly Understood

Despite metformin's success, its mechanism of action remained imperfectly understood. About a decade ago, researchers suggested that metformin reduces glucose synthesis by activating the enzyme AMPK. But this understanding was challenged by genetic experiments in 2010 by collaborators on the present Nature study. Coauthors Marc Foretz and Benoit Viollet from Inserm, CNRS, and Universit Paris Descartes, Paris, found that the livers of mice without AMPK still responded to metformin, indicating that blood glucose levels were being controlled outside of the AMPK pathway.

Taking another look at how glucose is regulated normally, the team knew that when there is no food intake and glucose decreases, glucagon is secreted from the pancreas to signal the liver to produce glucose. They then asked if metformin works by stopping the glucagon cascade.

The Nature study describes a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing 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.

From this new understanding of metformin's action, Birnbaum and colleagues surmise that adenylate cyclase could be a new drug target by mimicking the way in which it is inhibited by metformin. This strategy would bypass metformin's affect on a cell's mitochondria to make energy, and possibility avoid the adverse side effects experienced by many people who take metformin, perhaps even working for those patients resistant to metformin.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related biology news :

1. UCSB researchers perform pioneering research on Type 2 diabetes
2. NTU study finds ways to prevent muscle loss, obesity and diabetes
3. Notre Dame research may have important implications for combating diabetes
4. University of Chicagos Graeme Bell receives international diabetes prize
5. Joslin researchers increase understanding of genetic risk factor for type 1 diabetes
6. Arginine and proline enriched diet may speed wound healing in diabetes
7. Diabetes Management Provider ActiveCare Announces Cost Savings Of Over $4,000 Per Year Per Diabetic Member
8. Purple corn compound may aid in developing future treatments for Type 2 diabetes, kidney disease
9. Risk of developing diabetes higher in neighborhoods that arent walk-friendly: Study
10. Cystic fibrosis disrupts pancreas two ways in CF-related diabetes
11. Shedding new light on one of diabetes most dangerous complications
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Most-used diabetes drug works in different way than previously thought
(Date:3/31/2016)... Florida , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange ... potential users of its soon to be launched online ... ( https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide potential ... use of DNA technology to an industry that is ...
(Date:3/29/2016)... Florida , March 29, 2016 ... the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased ... in ink used in a variety of writing instruments, ... Buyers of originally created collectibles from athletes on LegacyXChange ... forensic analysis of the DNA. Bill ...
(Date:3/22/2016)... March 22, 2016 ... Sensors Market for Consumer Industry by Type (Image, ... Application (Communication & IT, Entertainment, Home Appliances, ... Forecast to 2022", published by MarketsandMarkets, the ... to reach USD 26.76 Billion by 2022, ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... , ... May 25, 2016 , ... Scientists at the ... options being tried for mesothelioma may be hampering the research that could lead to ... Click here to read it now. , The team evaluated 98 ...
(Date:5/25/2016)... , ... May 25, 2016 , ... ... Food and Drug Administration (FDA) has granted the company’s orphan drug designation request ... second orphan drug designation granted by the FDA. , Spinocerebellar ataxia is ...
(Date:5/24/2016)... ... ... Last week, Callan Capital, an integrated wealth management firm specializing in asset ... Diego Life Science event at the Estancia La Jolla Resort and Spa. , Over ... Dr. Rich Heyman, former CEO of Aragon and Seragon, and Faheem Hasnain, former CEO ...
(Date:5/23/2016)... ... May 23, 2016 , ... PrecisionAg® ... Farming in 2017 and Beyond. The paper outlines the key trends that are ... industry. , “We’ve witnessed a lot of highs and lows as the precision ...
Breaking Biology Technology: