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Pancreatic hormone linked with severe heart disease in obese and diabetic patients
Date:2/16/2012

patients who were overweight but not obese.

Using genetically engineered rats that secrete human amylin in the same proportion as it is found in obese people, the researchers determined that amylin oligomers attach to membranes of myocytes -- the heart-muscle cells that control heart beats. This made the membranes more porous to calcium, which changed myocyte contractility, altered the expression of vital proteins and, eventually, caused heart muscle cells to die.

"The significantly altered cardiac myocyte structure and function in the rats, along with the high levels of oligomers in the human heart tissue, strongly suggest that amylin is a major contributor to heart failure in obese and diabetic patients," Despa said.

Despa thinks that the link between cardiac amylin accumulation and heart disease has been overlooked because amylin circulates in relatively small amounts in blood, and because animals, including rats, that are often used in most studies of diabetic cardiac dysfunction do not normally express the form of amylin that aggregates and builds up in tissues.

The scientists now hope to find ways to curb amylin buildup in the heart before it has the chance to destroy muscle tissue.

"Drugs that block amylin from forming into toxic oligomers could significantly reduce the chances of heart failure," Despa said.

For the research, amylin protein accumulation was detected in human and rat heart tissues and cell cultures using immunohistochemistry, immunofluorescence and Western blot. Heart dysfunction in the rats was identified by studying the physiological performance of isolated myocytes and by measuring the expression of tell-tale proteins that deform cardiac muscle. The researchers used echocardiography and measurements of blood flow to assess heart tissue structure and performance and changes in myocardium contractions.


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Contact: Karen Finney
karen.finney@ucdmc.ucdavis.edu
916-734-9064
University of California - Davis Health System
Source:Eurekalert

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