Glucagon-Like Peptide-1 (GLP-1) and Dual GIP/GLP-1 Receptor Agonists in Renoprotection: A Study on Protein Expression and Phosphorylation Pathways in the Kidney

• Grant number: 25/04656-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Adriana Castello Costa Girardi
• Grantee: Gabriela Catão Diniz Braga
• Supervisor: Markus Rinschen
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 23/03620-1 - Role of endogenous GLP-1 in protecting against salt-sensitive hypertension, BP.DD

Abstract

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that play key roles in glucose homeostasis and exert renoprotective effects that extend beyond glucose control. These include antiproteinuric properties, anti-inflammatory actions, fibrosis suppression, and inhibition of systemic and intrarenal renin-angiotensin system (SRA) activity. However, the mechanisms underlying GLP-1-mediated renal protection remain unclear. This project aims to characterize the short- and long-term signaling pathways activated by endogenous GLP-1R and to compare renal responses to GLP-1 and dual GIP/GLP-1 receptor agonists. We will employ kidney proteomics and phosphoproteomics in rats subjected to acute and chronic GLP-1R blockade, followed by validation of target protein expression and phosphorylation in nephron segment suspension cultures treated with GLP-1 or co-treated withGLP-1 and GIP using immunoblotting. By identifying molecular pathways modulated by endogenous GLP-1 and GIP/GLP-1, this study will provide insights into their signaling mechanisms, roles in renal physiology and pathology, and their potential renoprotective effects. These findings may support the therapeutic use of GIP/GLP-1 receptor agonists in mitigating kidney injury and the progression of cardiorenal and metabolic diseases. (AU)