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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Safe glide at total engine failure with ELA-inside

27.02.2017 | Information Technology

Fraunhofer IFAM expands its R&D work on Coatings for protection against corrosion and marine growth

27.02.2017 | Materials Sciences

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>