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

• Grant number: 23/13695-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2024
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: DFG
• Principal Investigator: Luiz Osório Silveira Leiria
• Grantee: Luiz Osório Silveira Leiria
• Principal researcher abroad: Klaus Scholich
• Institution abroad: Goethe University Frankfurt, Germany
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Stefan Offermanns
• Associated research grant(s): 24/09790-9 - Deciphering the GPCRome that regulates energy metabolism, AP.R SPRINT

Abstract

The prevalence of metabolic diseases such as obesity and type-2 diabetes mellitus (T2DM) are increasing worldwide while the pharmacological treatments are limited. Previous results from our group showed that a thromboxane receptor (TP) antagonist reduced fasting blood glucose, circulating insulin levels and glucose tolerance similarly to metformin. Moreover, we found it 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 that is simultaneously antidiabetic, antilipemic and antithrombotic, we believe there is still room for significant improvement in anti-diabetes/obesity therapy. We believe that TP antagonism may be a therapeutic strategy for the oral treatment of T2DM and obesity while it provides important protection against thrombotic disorders. Thus, we hypothesized that TP receptor antagonist may produce its effects through TP-dependent and independent pathways and our goal is to identify how this drug exert its beneficial metabolic effects and identify the signaling pathways that are activated by this drug. (AU)