Scientists identify a therapeutic target for type 2 diabetes treatments

Researchers of the University of Barcelona (UB) described a new therapeutic target, the elF2a Kinase, for the treatment of type 2 diabetes and other metabolic diseases. The study, published in the scientific journal Diabetes, was led by the group of Manuel Vázquez Carrera, researcher of the Pharmacology and Pharmacognosy Unit of the Department of Pharmacology, Toxicology and Therapeutic Chemistry of the UB and IBUB, and CIBER for diabetes and metabolic diseases (CIBERDEM). There was also the participation of the UB-IBUB groups coordinated by Santiago Vázquez and Francesc Villarroya, and the teams of Ángela Valverde (CSIC-UAM, CIBERDEM) and Walter Wahli (University of Lausanne and Nanyang Technological University).

Type 2 diabetes is a long-term illness which affects the way in which our body uses glucose. The body is unable to use it properly and that makes it to be stuck in our blood. Diabetes which is not properly controlled can create problems in circulation, heart, eyes, kidneys and other organs.

The work was focused on the study of mice with FGF21 hormone, a regulating molecule of the glucose and lipid metabolism and involvement in the development of metabolic diseases such as diabetes. The aim of the study was to puzzle out the mechanisms that regulate the FGF21 expression in the liver to identify possible pharmacologic targets that shape the effects of this hormone.

The researchers identified the elF2a Kinase as a regulating molecule for the FGF21 expression. “The results show that the treatment with drugs that activate HRI increases FGF21 levels by reducing glucose intolerance and hepatic steatosis in mice that were feed a high-fat diet”, says Manuel Vázquez. “In addition, these properties suggest that HRI could be a pharmacologic target for the treatment of metabolic diseases, for its shaping effect on FGF212 levels”, he adds.

These results open a new research line to study HRI activators in the treatment for type 2 diabetes and other metabolic diseases. Actually, the researchers have presented a patent with the University of Barcelona. “The aim is to confirm the efficiency and safety of the drug HRI activators in pre-clinical studies” said the researcher.

Reference to the article

Zarei M., Barroso E.; Leiva R.; Barniol-Xicota M.; Eugènia Pujol, C.E.; Santiago Vázquez, X. P.; Pardo, V.; González-Rodríguez, A.; M. Valverde, A. M.; Quesada-López, T.; Villarroya, F.; Wahli, W.; Vázquez-Carrera, M. «Heme-Regulated eIF2α Kinase Modulates Hepatic FGF21 and is Activated by PPARβ/δ Deficiency». Diatetes, August 2016. DOI: 10.2337/db16-0155

Image: Researchers of the Pharmacology and Pharmacognosy Unit of the UB.