Navigation Links
Preventing diabetes damage: Zinc's effects on a kinky, two-faced cohort
Date:6/30/2011

ANN ARBOR, Mich.---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.


'/>"/>

Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

Related biology news :

1. Fluctuations before the fall: Predicting and preventing environmental collapse
2. Major breakthrough in preventing premature birth announced by NIH/WSU
3. Preventing heart problems while keeping a cool head
4. Preventing cancer, quite naturally
5. Preventing cells from getting the kinks out of DNA
6. Vaccines preventing pneumococcal disease protect African children with sickle-cell disease
7. Preventing gastric cancer with antibiotics
8. Preventing or reversing inflammation after heart attack, stroke may require 2-pronged approach
9. New finding in cell migration may be key to preventing clots, cancer spread
10. UC Davis research confirms benefits of calcium and vitamin D in preventing fractures
11. New study suggests minke whales are not preventing recovery of larger whales
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/13/2016)... , January 13, 2016 ... the addition of the  "India Biometrics ... & Forecast (2015-2020)"  report to ... ) has announced the addition of ... Market - Estimation & Forecast (2015-2020)" ...
(Date:1/11/2016)... -- higi, the leading retail and omni-channel community engagement platform ... mobile, today announced it has closed funding of ... --> --> The ... health platform – its network of health stations, ... services and programs to retail partners and healthcare ...
(Date:1/8/2016)... 2016 NXTD ), a company ... , a privately held leading direct seller of vacation ... 5000 fastest-growing company announced that on December 31, 2015, ... in Nxt-ID to develop a proprietary new wireless smart ... , a unique smart wallet that serves to securely ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... ... February 10, 2016 , ... HOLLOWAY AMERICA, a leading custom ... Rocky Mountain Chapter 21st Annual Vendor Exhibition on Thursday, February 18, 2016. The ... for its annual event, which will run from 3:00 p.m. - 8:30 p.m. ...
(Date:2/10/2016)... San Mateo, CA (PRWEB) , ... February 10, ... ... Registry of Multiplex Testing (PROMPT), a research registry built on the secure online ... in September 2014. More than 1,600 participants have joined the PROMPT study, which ...
(Date:2/10/2016)... ... , ... Cenna Bioscience Inc., an emerging biopharmaceutical company focused on the discovery ... has been selected to present at the Cavendish Global Health Impact Forum taking place ... purpose of the Forum is to help family offices and foundations develop and implement ...
(Date:2/9/2016)... , Feb. 9, 2016  Regenicin, Inc. ... company specializing in the development and commercialization of ... damaged tissues and organs, recently reported the Company,s ... first quarter of 2016. Lonza America ... new 2015 fiscal year in the process of ...
Breaking Biology Technology: