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Nature Publication Reports on Key Role of Bile Acids in Glucose Metabolism and Insulin Signaling
Date:8/7/2008

Intercept Pharmaceuticals is Advancing Bile Acid-Derived Small Molecules

with Potential Applications in Treating Metabolic Diseases

NEW YORK, Aug. 7 /PRNewswire/ -- Historically, bile acids have been recognized primarily as natural detergents that regulate the absorption of dietary lipids and cholesterol homeostasis. However, recent research advances provide evidence that bile acids have broader systemic endocrine functions, acting as important mediators of glucose metabolism and insulin signaling. The featured article in the current issue of Nature Reviews Drug Discovery (Vol. 7, Number 8, August 2008) describes why bile acid receptors are promising targets for drug development in obesity, type 2 diabetes, atherosclerosis and other chronic metabolic disorders such as nonalcoholic steatohepatitis.

Highlights of the article, "Targeting bile acid signaling for metabolic diseases," authored by Drs. Charles Thomas, Roberto Pellicciari, Mark Pruzanski, Johan Auwerx and Kristina Schoonjans, include:

-- Bile acids serve as metabolic integrators, activating major signaling pathways regulated by nuclear hormone receptors including the farnesoid X receptor (FXR) and G protein-coupled receptors (GPCRs) such as TGR5.

-- Bile acids play a major role in lipid metabolism and homeostasis. For example, bile acid activation of FXR results in a decrease in serum triglyceride levels.

-- The activation of TGR5 by bile acids increases energy expenditure and reduces diet-induced obesity. Conversely, "knockout" animal models engineered to lack TGR5 show a tendency towards weight gain.

-- Bile acids have broad effects on glucose homeostasis, including a decrease in gluconeogenesis (glucose synthesis by the liver). These effects have been attributed primarily to activation of FXR. Additionally, mice that lack FXR have impaired glucose tolerance and are insulin-resistant.

Dr. Schoonjans, Ph.D., a group leader at the Ecole Polyte
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SOURCE Intercept Pharmaceuticals
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