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:5/24/2016)... , May 24, 2016 Ampronix facilitates superior patient care by providing unparalleled ... medical LCD display is the latest premium product recently added to the range of ... ... ... Sony 3d Imaging- LCD Medical Display- Ampronix News ...
(Date:5/9/2016)... , UAE, May 9, 2016 ... it comes to expanding freedom for high net worth ... Even in today,s globally connected world, there is still ... system could ever duplicate sealing your deal with a ... second passports by taking advantage of citizenship via investment ...
(Date:4/26/2016)... LONDON , April 26, 2016 ... a product subsidiary of Infosys (NYSE: ... to integrate the Onegini mobile security platform with ... http://photos.prnewswire.com/prnh/20151104/283829LOGO ) The integration will ... to access and transact across channels. Using this ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , ... June 23, 2016 , ... ... YM (Yeast and Mold) microbial test has received AOAC Research Institute approval 061601. ... microbial tests introduced last year,” stated Bob Salter, Vice President of Regulatory and ...
(Date:6/23/2016)... ... , ... Supplyframe, the Industry Network for electronics hardware design ... Located in Pasadena, Calif., the Design Lab’s mission is to bring together inventors ... and brought to market. , The Design Lab is Supplyframe’s physical representation of ...
(Date:6/23/2016)... , June 23, 2016  Blueprint Bio, a company ... to the medical community, has closed its Series A ... Nunez . "We have received a commitment ... capital we need to meet our current goals," stated ... us the runway to complete validation on the current ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® ... provides a free webinar on Performing Quality Investigations: Getting to Root ... CT at no charge. , Incomplete investigations are still a major concern to ...
Breaking Biology Technology: