Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Preventing diabetes damage: Zinc's effects on a kinky, two-faced cohort

01.07.2011
In type 2 diabetes, a protein called amylin forms dense clumps that shut down insulin-producing cells, wreaking havoc on the control of blood sugar. But zinc has a knack for preventing amylin from misbehaving.

Recent research at the University of Michigan offers new details about how zinc performs this "security guard" function. The findings appear in the July 8 issue of the Journal of Molecular Biology.

Amylin is something of a two-faced character. In healthy people who have normal levels of zinc in the insulin-producing islet cells of the pancreas, amylin actually pitches in to help with blood sugar regulation, says Ayyalusamy Ramamoorthy, a U-M professor of chemistry and of biophysics in the College of Literature, Science, and the Arts. In fact, an analog of amylin called Symlin is used in conjunction with insulin to manage blood sugar levels in diabetics.

This good behavior on amylin's part comes about because zinc acts like a security guard at a rock concert, whose job is keeping fans from turning troublesome and destructive. In molecular terms, zinc prevents amylin—also known as Islet Amyloid Polypeptide (IAPP)—from forming harmful clumps similar to those found in Alzheimer's, Parkinson's, Huntington's and various other degenerative diseases.

But in a zinc-starved cellular environment of someone with type 2 diabetes, amylin has no watchful guard to rein it in. It's free to clump together with other amylin molecules in the molecular equivalent of a gang.

The clumping ultimately leads to the formation of ribbon-like structures called fibrils, and because fibril formation has been linked to a number of human diseases, it was long assumed that fibrils themselves were toxic. But accumulating evidence now suggests that the actual culprits may be shorter snippets that assemble in the process of forming full-length fibrils. For this reason, it's important to understand the whole aggregation process, not just the structure of the final fibril.

Ramamoorthy and colleagues are trying to better understand exactly how zinc interacts with amylin, in hopes of finding ways of treating or preventing type 2 diabetes and other diseases associated with aging. In earlier work, they showed that when zinc binds to amylin, at a point near the middle of the amylin molecule, the amylin molecule kinks, which interferes with the formation of toxic clumps. In the current work, they show that the binding of zinc in the middle makes one end of the amylin molecule, called the N-terminus, become more orderly.

"This is significant, because the N-terminus is very important in clump formation and amylin toxicity," Ramamoorthy said.

In addition, the researchers found that before amylin can begin forming fibrils, zinc must be rousted from its nesting place. This eviction is costly in energetic terms, and the sheer expense of it discourages fibril formation. And because a single zinc molecule can bind to several amylin molecules, it ties up the amylin in assemblages that, unlike certain other aggregations, are not intermediates in the pathway that leads to fibril formation.

However zinc, like amylin, has a dual nature. At conditions similar to those outside islet cells, where even a tiny amount of amylin aggregates in the blink of an eye, zinc inhibits fibril formation. But in conditions resembling the inside of the cell, the inhibitory effect begins to wane and other factors, like insulin, take on zinc's security guard duties. Ramamoorthy's group found that this happens because amylin has not one, but two binding sites for zinc. Zinc prefers to bind at the first site—the one in the middle of the amylin molecule, where its binding discourages fibril formation. But when there's too much zinc around, all the binding sites in the middle positions are occupied and zinc must attach to amylin at the second site, which counteracts the effect of the first site. This may explain why decreased levels of insulin—the backup security guard—inside islet cells of diabetics result in islet cell death.

The experiments described in the Journal of Molecular Biology paper were all done in an artificial environment, not a living organism where zinc levels constantly fluctuate. In future experiments, Ramamoorthy hopes to more closely approximate natural conditions in order to better understand how amylin interacts with islet cells and what triggers its toxicity toward the cells. The results of these studies will facilitate the development of metal-based therapies for type 2 diabetes, similar to the promising metal-based drugs developed for Alzheimer's and other neurodegenerative diseases, Ramamoorthy said.

Ramamoorthy's coauthors in the paper are undergraduate student Samer Salamekh, postdoctoral fellows Jeffrey Brender and Suk-Joon Hyung, former graduate student Ravi Prakash Reddy Nanga, NMR specialist Subramanian Vivekanandan and assistant professor of chemistry Brandon Ruotolo

The National Institutes of Health provided funding for the research.

Contact: Nancy Ross-Flanigan
Phone: (734) 647-1853

Nancy Ross-Flanigan | EurekAlert!
Further information:
http://www.umich.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>