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Prescription Diabetes Drugs
Posted by admin in Prescription Diabetes Drugs on February 24th, 2011
TGR5, a G protein-coupled receptor expressed in brown adipose tissue and muscle, may be a novel therapeutic target for Type 2 diabetes and obesity or “diabesity,” research indicates.
In preclinical and in vitro studies, a pharmacologic selective TGR5 activator brought about an increase in muscle energy expenditure, a property with “therapeutic potential,” according to the study authors.
The work was undertaken by Johan Auwerx (Ecole Polytechnique Federale de Lausanne, Switzerland) and international collaborators and focused on the protein TGR5, which upon activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity.
Through a combination of pharmacological and genetic gain- and loss-of-function studies, the researchers found that TGR5 controls the secretion of glucagon-like peptide (GLP)-1 from enteroendocrine cells in the gut.
The therapeutic relevance of GLP-1 is well-established, say the researchers, and several drugs exploiting the properties of this hormone are already in advanced clinical development.
When administered to obesity-prone mice, TGR5 resulted in improved liver and pancreatic function as well as enhanced glucose tolerance, Auwerx et al report in Cell Metabolism.
Most importantly, administration of a specific TGR5 agonist, INT-777, induced GLP-1 release as well as leading to an increase in the intracellular ADP/ATP ratio and a rise in intracellular calcium mobilization.
Taken together, the results indicate that TGR5 activation “counteracts the metabolic dysfunction associated with diabesity,” say the researchers, through an increase in energy expenditure and incretin secretion.
“This leads us to conclude that TGR5 agonists could represent potential promising agents for the management of diabesity, along with associated disorders such as nonalcoholic steatohepatitis.” MedWire Diabetes, lipidology AstraZeneca Global v2 - Cardiovascular News Medical Disease_group: diabetes mellitus, dyslipidemia Drug provider: none Baylor: lipid
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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