GLP-1 and diabetic nephropathy share key molecular targets

Glucagon-like peptide-1 (GLP-1) receptor agonists provide renoprotective benefits in diabetes, yet the molecular mechanisms linking GLP-1 signaling to diabetic nephropathy remain poorly defined. This study aimed to identify shared molecular targets between GLP-1 activity and diabetic kidney disease by integrating protein targets of GLP-1 from UniProt with disease-associated genes from GeneCards. The overlapping gene set was analyzed using STRING and Cytoscape^® with MCODE clustering, followed by GO and KEGG enrichment through the clusterProfiler package. Molecular docking with HADDOCK was employed to validate structural interactions between GLP-1 and central network proteins. We identified 17 shared genes, including STAT3, EP300, MAPK1, and INSR, which formed a densely connected cluster enriched in pathways related to insulin response, hypoxia adaptation, apoptosis, and glucose metabolism. Docking analysis demonstrated direct and favorable binding of GLP-1 to STAT3, PIK3R1, and EP300, suggesting noncanonical intracellular mechanisms involving transcriptional regulation and epigenetic modulation. These findings reveal a novel convergence between GLP-1 signaling and diabetic nephropathy pathways, providing mechanistic insights that guide the experimental determination of the underlying molecular interactions. This framework may ultimately contribute to the refinement of renal therapies based on GLP-1 modulation.