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In mice, drug protects against diabetes and atherosclerosis

Blocking a single protein with an experimental drug prevented and treated both type 2 diabetes and atherosclerosis in laboratory mice that had been fed unhealthy diets and were genetically predisposed to these common killers, according to an article published online at Nature on June 6, 2007. The team was led by senior author Gökhan Hotamisligil, chair of the Department of Genetics and Complex Diseases at the Harvard School of Public Health (HSPH). Lead author was Masato Furuhashi, research fellow in the department.

In earlier studies, Hotamisligil's lab members researched mice lacking two lipid-binding proteins, aP2 and mal1. When these mice were fed a high-cholesterol or high-fat diet, the expected signs of metabolic diseases such as atherosclerosis, type 2 diabetes, and fatty liver disease never developed. Recently, researchers in Hotamisligil's lab and at the Garvan Institute of Medical Research in Australia also demonstrated that these genes were critical in the development of asthma, another disease associated with obesity.

In this new paper, researchers from HSPH, Bristol-Myers Squibb, and elsewhere describe how a designer compound mimics many of these protective effects in mice, conferring substantial immunity to diabetes, heart disease, and other metabolic problems. This immunity takes place even if the animals are severely obese or have high amounts of cholesterol and consume dangerously fatty foods. Use of the compound not only appears to prevent the development of these diseases, but also to reverse the symptoms of these illnesses in mice.

"To have this chemical in hand and to replicate the effects of genetic manipulation is a huge milestone and an incredible source of excitement," said Hotamisligil, Professor of Genetics and Complex Diseases. "This drug is very effective in treating diabetes and heart disease in mice at the same time, and we believe it may turn out to be protective against asthma and other metabolic disorde
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Source:Harvard School of Public Health


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