Data from: 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
Gene Ontology 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 non-canonical 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.