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Mechanism Behind How Diabetes Drugs Raise Heart Failure Risk Identified

by Rajashri on Jun 24 2009 7:44 PM

The mechanism behind how a class of diabetes drugs increases the risk of heart failure may be explained by a new study.

Thiazolidinediones (TZDs) have been controversial since a 2007 analysis of Avandia (rosiglitazone), a TZD made by GlaxoSmithKline, suggested that patients taking it are at higher risk of heart attack.

Less controversial are data linking TZDs with heart failure, a distinct condition in which the heart cannot pump enough blood through the body.

"We already knew if you had heart failure you probably should not be taking these drugs, but this paper provides an additional explanation why," Nature quoted Clay Semenkovich, an endocrinologist at the Washington University School of Medicine in St Louis, Missouri, as saying.

In the study, the researchers found that a molecule activated by TZDs, called PPAR-?, underlies one aspect of heart failure.

When the authors started the study, they were not thinking about diabetes drugs. Instead, they wanted to know what happens when tissues enlarge.

Wilhelm Krek, a cancer biologist at the Swiss Federal Institute of Technology in Zurich, said: "If a cancer grows, it outstrips its nutrient and oxygen supply."

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Researchers thought that something similar might happen when the heart enlarges, as it often does after a heart attack or during chronic high blood pressure.

The increased size enables the heart initially to pump more blood but can ultimately weaken the organ.

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Enlarged hearts labour to get oxygen, and they switch from burning fat to glucose, which can provide energy without oxygen but is less efficient.

Heart cells can then weaken, accumulate fat and eventually commit suicide.

Researchers found that PPAR-? might lead in this downfall.

They found high levels of PPAR-? in heart tissue from people with heart failure, as well as in hearts of mice experimentally manipulated to model the condition.

When they knocked PPAR-? out in mouse heart cells, the cells did not accumulate fat and did not die.

The study has been published in the June issue of Cell Metabolism.

Source-ANI
RAS


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