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Doubling down against diabetes
Date:11/13/2012

This press release is available in German.

A collaboration between scientists in Munich, Germany and Bloomington, USA may have overcome one of the major challenges drug makers have struggled with for years: Delivering powerful nuclear hormones to specific tissues, while keeping them away from others.

The teams led by physician Matthias Tschp (Helmholtz Zentrum Mnchen, and Technische Universitt Mnchen) and chemist Richard DiMarchi (Indiana University) used natural gut peptides targeting cell membrane receptors and engineered them to carry small steroids known to act at the cell nucleus. DiMarchi and Tschp hoped that such "turbo-charged" hormone hybrids would only deliver their steroid inside cells, where their specific peptide receptor was expressed at the surface.

Both teams had been working together for years to discover new ways to treat obesity and diabetes. They therefore started out with the gut hormone glucagon-like peptide-1, which is known to act at pancreas and brain cells to improve insulin secretion, blood glucose, and body weight. They engineered these peptides to reversibly bind the female sex steroid, estrogen, which is also known to confer powerful metabolic benefits at some of the same target cells. In the past, pharmacologists had been unable to utilize such benefits as high doses of systemic estrogen can also powerfully affect reproductive organs and increase cancer risk.

Using their GLP-1/estrogen-conjugates however, DiMarchi and Tschp found that they were able to multiply metabolic benefits in mice, without apparent side effects on estrogen-sensitive reproductive organs such as the uterus. They also found no impact of their "turbo-charged" gut peptides on growth of estrogen-sensitive tumors. Genetic studies at the same time however uncovered clear estrogen effects in pancreas and brain tissue of mice treated with
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Contact: Tina Heun-Rattei
Heun@zv.tum.de
Technische Universitaet Muenchen
Source:Eurekalert

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