Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists uncover startlingly new functional details of common anti-diabetic drugs

07.04.2014

The findings could guide design of future therapies

Scientists thought they basically knew how the most common drugs used to treat type 2 diabetes worked, but a new study from the Florida campus of The Scripps Research Institute (TSRI) reveals unexpected new aspects of the process. These findings could eventually lead to more potent anti-diabetic drugs with fewer serious side effects.


Douglas Kojetin, Ph.D., is an associate professor at the Scripps Research Institute, Florida campus.

Credit: Photo courtesy of the Scripps Research Institute

The study was published in the April 7, 2014 issue of the journal Nature Communications.

The most common type 2 diabetes treatments are known as insulin-sensitizing drugs, which improve how the body responds to glucose or sugar. These drugs mimic naturally occurring compounds that bind to a specific intracellular receptor (peroxisome proliferator-activated receptor-γ or PPARG), altering its activity.

While these drugs were widely thought to bind to a single site on the receptor, the new study shows they also bind to an alternative site, leading to unique changes in receptor shape, which affects interaction with co-regulating protein partners and gene expression.

Douglas Kojetin, an associate professor at TSRI who led the study, called the discovery serendipitous—and revealing.

"It turns out that binding to PPARG is far more complex than anyone previously understood," he said. "You don't have to displace the naturally occurring ligand [binding partner] with a synthetically designed drug to regulate the receptor because you have this alternative site."

Kojetin and his colleagues made the alternative binding site discovery using a far simpler mapping technique than had previously been applied to determine the receptor's structure.

"We used a technique that yields easy-to-interpret results, one that you wouldn't normally use to look at how drugs bind a receptor," said Research Associate Travis Hughes, the first author of the study and a member of Kojetin's lab. "Instead of finding one site, we realized we had two and wanted to know what the second one was doing."

The scientists note that while they don't yet know the full effect of the alternate binding site's function, it might provide a clue to insulin-sensitizing drugs' adverse effects, which include risk of bone loss and congestive heart failure.

"The question going forward is 'Does this alternative site contribute to side effects, beneficial effects or both?'" said Kojetin. "Knowledge of this alternate binding site may help produce a new generation of anti-diabetic drugs."

###

In addition to Kojetin and Hughes, authors of the study, "An Alternate Binding Site for PPARγ Ligands," include Pankaj Kumar Giri, Ian Mitchelle S. de Vera, David P. Marciano, Dana S. Kuruvilla, Youseung Shin, Anne-Laure Blayo, Theodore M. Kamenecka and Patrick R. Griffin of TSRI; and Thomas P. Burris of St. Louis University.

The study was supported by the state of Florida, the James and Esther King Biomedical Research Program, the Florida Department of Health (grant number 1KN-09) and the National Institutes of Health (grant numbers DK101871 and DK097890).

Eric Sauter | EurekAlert!
Further information:
http://www.scripps.edu

Further reports about: Health Scripps TSRI compounds drugs failure peroxisome regulate technique

More articles from Life Sciences:

nachricht Heidelberg Researchers Find Unusually Elastic Protein
23.01.2015 | Ruprecht-Karls-Universität Heidelberg

nachricht Early human ancestors used their hands like modern humans
23.01.2015 | Max Planck Institute for Evolutionary Anthropology, Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Anzeige

Anzeige

Event News

2000 Erziehungswissenschaftler an der Uni Kassel erwartet

19.01.2015 | Event News

How are Europe’s landscapes influenced by the changing energy sector?

19.01.2015 | Event News

Value chain driven development of rural areas in Eastern Europe

22.12.2014 | Event News

 
Latest News

Rare neurological disease shines light on health of essential nerve cells

23.01.2015 | Health and Medicine

California's policies can significantly cut greenhouse gas emissions through 2030

23.01.2015 | Ecology, The Environment and Conservation

Exotic, gigantic molecules fit inside each other like Russian nesting dolls

23.01.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>