Investigation on the pharmacological aspects underlying the antidiabetic effects of a thromboxane receptor (TP) antagonist

• Applicants: Professor Dr. Stefan Offermanns; Professor Dr. Klaus Scholich
• Subject Area: Pharmacology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 540675608

The prevalence of metabolic diseases such as obesity and type-2 diabetes mellitus (T2DM) are increasing worldwide while pharmacological treatments are still limited. Previous results from our group showed that the thromboxane receptor (TP) antagonist seratrodast reduced fasting blood glucose, insulin levels and glucose tolerance similarly to metformin. Moreover, seratrodast decreased LDL and triglyceride levels in a higher magnitude than metformin. This drug is also known for its anti-platelet effect. Considering that there is still no drug available which has simultaneously anti-diabetic, anti-lipemic and anti-thrombotic effects, we believe there is still room for significant improvement in anti-diabetes/obesity therapy. TP antagonism may provide a novel therapeutic strategy for the oral treatment of T2DM and obesity while it provides important protection against thrombotic disorders. Preliminary results show that seratrodast affects lipid metabolism even in cells that do not express the TP receptor. Therefore, the hypothesis of the application is that the TP antagonist seratrodast exerts its effects via TP-dependent and -independent pathways. Our goal is therefore to understand how this drug exerts its beneficial metabolic effects and to identify the signaling pathways that mediate these effects.

• DFG Programme: Research Grants
• International Connection: Brazil
• Partner Organisation: Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP
• Cooperation Partner: Professor Luiz Osorio Leiria, Ph.D.