New molecule discovery may help combat Type 2 diabetes, obesity

WASHINGTON - Type 2 diabetes can be treated, and weight gain reduced by activating a protein called TGR5, according to a new study.

Swiss researchers Dr. Kristina Schoonjans and Prof. Johan Auwerx, both from the Ecole Polytechnique Federale de Lausanne, have revealed that they have characterized the metabolic properties of a selective TGR5 activator (INT-777), a drug with a promising future for the treatment of diabetes and obesity.

The researchers previously found that bile acids (endogenous molecules involved in digestion), via the activation of TGR5 in muscle and brown adipose tissue, could boost energy expenditure and prevent or reverse diet-induced obesity in mice.

In the most recent study they carried out with American and Italian collaborators, Dr Kristina Schoonjans and Prof. Johan Auwerx went further in studying the role of TGR5 in the gut, where TGR5 is expressed in cells specialized in the production of gut-derived hormones.

The study showed that in the so-called enteroendocrine cells, TGR5 controls the secretion of the hormone Glucagon-Like Peptide 1 (GLP-1), which plays a critical role in the control of pancreatic function and the regulation of blood sugar levels.

It further revealed that under laboratory conditions, the compound INT-777 could effectively treat diabetes and reduce fat mass.

The authors have furthermore shown that these effects were related to the increase in both GLP-1 secretion and energy expenditure.

Charles Thomas, first author of the study, said that this work is of great interest because it could herald a new approach in the treatment of type 2 diabetes and obesity.

“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),” he said.

In this study, the authors propose a third therapeutic option based on increasing GLP-1 secretion via administration of TGR5 agonist therapy.

A research article describing the study has been published in the journal Cell Metabolism.

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