An orally administered molecule (EPB-53) reduces glucose intolerance and improves type 2 diabetes and non-alcoholic fatty liver disease in mice by increasing the endogenous levels of a hormone, called Fibroblast growth factor 21 (FGF21), which in turn combats these pathologies, according to a study carried out by researchers from the Universitat de Barcelona (UB) and the Center of Biomedical Research in Network for Diabetes and Associated Metabolic Diseases (CIBERDEM), published in the British Journal of Pharmacology.
It was already known that FGF21 was a therapeutic target to treat these diseases —which main risk factors are obesity and insulin resistance— but drugs based on analogues of this protein had to be administered subcutaneously, and in some cases have adverse effects such as generating bone loss, and cause an increase in blood pressure and heart rate.
An oral drug without adverse effects
The researchers showed that oral administration of EPB-53 to mice fed a high-fat diet raised their levels of FGF21 in plasma and liver, thanks to the fact that this molecule activates HRI (hemorrhaged EIF2-alpha kinase), a kinase that in turn activates a transcription factor that intervenes in the increase of FGF21 and decreases hepatic steatosis and glucose intolerance in animals, according to Manuel Vázquez Carrera, group leader of CIBERDEM.
The results suggest that using this new compound that induces FGF21 may be useful in the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease with an effect similar to that of subcutaneous analogs, but avoiding its side effects. Vázquez Carrera has stated that they are currently working on the development of new activators of HRI that present better pharmacokinetic characteristics for the treatment of both diseases.
Source: Agencia ID