The research team of experimental hepatology from the NETPHARM project (OP JAC) recently discovered a novel mechanism of the antidiabetic effect of the first dual Farnesoid X receptor antagonist/TGR5 agonist 7β-isopropylchenodeoxycholic acid.
This compound was discovered by researchers from Charles University, specifically from the Faculty of Pharmacy in Hradec Králové (Prof. Pávek) and the Faculty of Medicine in Hradec Králové (Dr. Štefela, Prof. Mičuda, and Prof. Kučera) and synthesized by Dr. Kudová's group at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences. The results have been published in the Pharmacological Research journal.
The researchers described the effects of the compound on glucose homeostasis using a glucose tolerance test in mice fed a Western diet and omics analyses. The glucose-lowering mechanism was found to be mediated by GLP-1 release, the regulation of glucose transporter expression, and the regulation of relevant genes involved in glucose metabolism in intestinal, hepatic, white adipose, and renal tissues, as well as in human NCI-H716 and murine GLUTag L cell lines.
DOI: 10.1016/j.phrs.2025.107950
These data suggest a novel combined intervention in diabetes mellitus using the first steroidal FXR antagonists/TGR5 agonists for managing hyperglycemia.
The research was supported by the project New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM.
„The project New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM, project ID CZ.02.01.01/00/22_008/0004607, is co-funded by the European Union.“
