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New look identifies crucial clumping of diabetes-causing proteins
Date:11/12/2013

MADISON People get type 2 diabetes. So do cats. But rats don't, and neither do dogs.

Subtle differences in the shape of proteins protect some and endanger others.

"All mammals make this same protein called amylin, and it only differs a little bit from species to species," says Martin Zanni, a University of WisconsinMadison chemistry professor. "The mammals that get type 2 diabetes, their amylin proteins aggregate in the pancreas into plaque that kills the cells around them. As a result, you can't make insulin."

Without insulin, hungry cells can't tap sugar in the bloodstream for energy, and high blood sugar levels cause type 2 diabetes and its complications stroke, nerve damage and kidney disease among them.

Animal species that don't get type 2 diabetes find a way to keep plaque from forming in their pancreas and disrupting insulin production. Describing how their amylin proteins differ may provide a target for new treatments for diabetes and other plaque-involved disease such as Alzheimer's and Parkinson's.

A study published today by Zanni and collaborators in the Proceedings of the National Academy of Sciences paints that target on small clumps of mis-folding proteins in the middle of the plaque formation process.

"For about 30 years, we thought this problem was solved, because a lot of experiments pointed to the middle part of amylin molecules as the cause," Zanni says.

Named for its amino acid structure, the FGAIL regions of amylin proteins were believed to lock together "like boards in a wood floor," Zanni says into rigid sheets. The sheets, called beta-sheets, break apart, forming the dangerous plaque.

But experiments published in 2007 showed that the FGAIL section of amylin is floppy and loose, like a loop of rope. "This result made no sense compared to the 30 years of prior studies," Zanni says. "Why should the small differences in the amylin protein of various mamma
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Contact: Martin Zanni
zanni@chem.wisc.edu
608-262-4783
University of Wisconsin-Madison
Source:Eurekalert

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