New insights into cause of diabetes emerge from U-M research

Apr 30, 2008

University of Michigan researchers have new clues to what goes awry at the cellular level in type 2 diabetes.

Their results, published in this week's issue of the Journal of the American Chemical Society (JACS), challenge conventional views of how the disease is initiated and may lead to development of drugs to treat aging-related diseases, as well as diabetes.

One of the most striking hallmarks of type 2 diabetes is the presence of clumped protein fibers called amyloids in the insulin-producing cells of the pancreas. Previous research has suggested that amyloid formation somehow damages the membranes surrounding those cells, killing the cells and precipitating diabetes.

But associate professor of chemistry and biophysics Ayyalusamy Ramamoorthy and co-workers show in the new study that membrane damage can occur independently of amyloid formation and that the protein involved, known as Islet Amyloid Polypeptide Protein (IAPP), has separate regions responsible for amyloid formation and membrane disruption.

"It was already known that amyloid fibers themselves are not especially harmful to cells, but it was thought that the process of amyloid formation might generate toxic intermediates that caused membrane damage. This issue has been the subject of active debate," Ramamoorthy said.

By breaking off one end of the protein and testing the resulting fragment's properties, the U-M group learned that the fragment can disrupt membranes and cause cell death as effectively as the full-length protein, without forming amyloids.

Then, comparing the human form of the IAPP with the rat version, which does not cause cell death, the researchers found that a difference of a single amino acid (protein building block) accounts for the toxicity. In conjunction with chemistry and pharmacology professor Robert T. Kennedy, Ramamoorthy is now studying the protein in living cells and obtaining the same results as with the model cell membranes used in the recent JACS paper.

Although IAPP is believed to contribute to the development of type 2 diabetes, drugs to suppress the role of IAPP in diabetes have not yet been developed, mainly because the molecular mechanism by which IAPP becomes toxic has been a mystery. In addition, the presence of toxic and non-toxic forms of the same protein in human body considerably complicates the discovery of what makes the protein toxic.

"Interestingly, this is exactly the same problem that has been limiting research progress in discovering drugs to treat other devastating aging-related amyloid diseases like Alzheimer's, Parkinson's, Huntington's and mad cow disease," Ramamoorthy said. "Our key finding of a version of the protein that exists in only one stable toxic form considerably simplifies the search for compounds to prevent these diseases."

Next, the researchers plan to use atomic-level molecular imaging solid-state NMR techniques to make nanoscopic movies to further elucidate the causes of type 2 diabetes. In addition, they plan to explore how changes in cell membrane molecules with age contribute to the development of aging-related diseases.

Source: University of Michigan

Explore further: Testing time for stem cells

add to favorites email to friend print save as pdf

Related Stories

MasterCard, Zwipe announce fingerprint-sensor card

3 hours ago

On Friday, MasterCard and Oslo, Norway-based Zwipe announced the launch of a contactless payment card featuring an integrated fingerprint sensor. Say goodbye to PINs. This card, they said, is the world's ...

Plastic nanoparticles also harm freshwater organisms

5 hours ago

Organisms can be negatively affected by plastic nanoparticles, not just in the seas and oceans but in freshwater bodies too. These particles slow the growth of algae, cause deformities in water fleas and impede communication ...

Atomic trigger shatters mystery of how glass deforms

5 hours ago

Throw a rock through a window made of silica glass, and the brittle, insulating oxide pane shatters. But whack a golf ball with a club made of metallic glass—a resilient conductor that looks like metal—and the glass not ...

US company sells out of Ebola toys

13 hours ago

They might look tasteless, but satisfied customers dub them cute and adorable. Ebola-themed toys have proved such a hit that one US-based company has sold out.

UN biodiversity meet commits to double funding

13 hours ago

A UN conference on preserving the earth's dwindling resources wrapped up Friday with governments making a firm commitment to double biodiversity aid to developing countries by 2015.

Recommended for you

Testing time for stem cells

1 hour ago

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

21 hours ago

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments : 0