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New Molecule Combats Diabetes and Obesity by Increasing GLP-1

Posted: Wednesday, September 09, 2009

We now have drugs that can replace the GLP-1 hormone and we have drugs that can reduce the destruction of GLP-1. Now we may have a drug that increases the production of GLP-1.

The rise in obesity and the onset of Type 2 diabetes is increasing at epidemic rates, affecting more than 180 million people worldwide. A group from the Ecole Polytechnique Fédérale de Lausanne (EPFL) may have found a new weapon in the fight against these disorders.

The study demonstrates that activation of the protein TGR5 can treat Type 2 diabetes and reduce weight gain. In collaboration with Prof. Roberto Pellicciari and colleagues at the University of Perugia, Italy, and Intercept Pharmaceuticals, New York, the group at the EPFL, led by Dr. Kristina Schoonjans and Prof. Johan Auwerx, have identified a selective molecule that can activate the TGR5 protein. It is called INT-777.

The authors based their research on knowledge that TGR5 controls the secretion of the gut-derived hormone Glucagon-Like Peptide 1 (GLP-1), which plays a critical role in pancreatic function and the regulation of blood sugar levels. In collaboration with Prof. Pellicciari, who designed the TGR5 activator INT-777, the group at the EPFL has shown under laboratory conditions that this compound can effectively treat diabetes and reduce fat mass.

Charles Thomas, first author of the study, was quoted as saying, "Recently, two classes of drugs exploiting the properties of the hormone GLP-1 have been marketed for the treatment of Type 2 diabetes. The first strategy aims to increase the blood levels of GLP-1 by limiting its degradation in the body. The second is to mimic the effects of GLP-1 using drugs activating the GLP-1 receptor (GLP-1R). "

In the current study, the authors propose a third therapeutic option based on increasing GLP-1 secretion by administering INT-777. The researchers found that, in addition to stimulating the secretion of GLP-1, INT-777 activated TGR5 in other tissues leading to an increase in energy expenditure and a resulting reduction in fat mass and obesity.

Source: Diabetes In Control: Cell Metabolism, September 2, 2009

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