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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wicik, Z; Nowak-Szwed, A; Eyileten, C; Sourij, H; von, Lewinski, D; Kistkins, S; Borkowska, J; Postuła, M.
Integrative gene-metabolite network analysis of GLP-1 receptor agonists and related incretin pathways in cardiometabolic health.
NPJ Syst Biol Appl. 2025; 11(1):144
Doi: 10.1038/s41540-025-00619-6
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- Co-Autor*innen der Med Uni Graz
- Sourij Harald
- von Lewinski Dirk
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- Abstract:
- Glucagon-like peptide-1 (GLP-1) is a hormone known for its critical functions in managing blood sugar and offering cardiovascular benefits. Our study focuses on Glucagon Like Peptide 1 Receptor (GLP1R) agonists that act beyond glycemic control in cardiovascular and metabolic health. A comprehensive bioinformatic analysis was conducted, incorporating GLP1R, Gastric Inhibitory Polypeptide Receptor (GIPR), Gastric Inhibitory Polypeptide (GIP) and glucagon receptor (GCGR) to assess the effects of GLP1R agonists on gene and metabolite interactions. Interaction network analysis revealed 130 common genes among GLP1R, GLP1R/GIPR, GLP1R/GIP, and GLP1R/GIPR/GCGR associated with diabetes-related processes, including obesity and hyperglycemia. Enriched terms related to cardiovascular diseases, such as hypertension, calcium regulation in cardiac cells, and amino acid accumulation-induced mTOR activation. We also observed enrichment in gene sets linked to longevity and less recognized terms like fatty liver disease. In GLP1R/GIP, behavior-related terms and gastric acid secretion were identified; GLP1R/GIPR/GCGR linked to fibrosarcoma, thought/speech disturbances, and adipogenesis. The metabolite-gene layer revealed enrichment in galactose metabolism, platelet homeostasis, and nitric-oxide pathways. We found that GLP1R agonists network-level associations are stronger with heart diseases than sodium-glucose co-transporter 2 inhibitors, suggesting greater therapeutic benefits. Integrating networks with metabolites highlighted key interactors and clarified GLP1R agonists' mechanisms and therapeutic potential.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Incretins - metabolism
- Glucagon-Like Peptide-1 Receptor Agonists - administration & dosage
- Computational Biology - methods
- Glucagon-Like Peptide-1 Receptor - metabolism, genetics
- Gene Regulatory Networks - administration & dosage
- Receptors, Glucagon - metabolism, genetics
- Cardiovascular Diseases - genetics, metabolism
- Receptors, Gastrointestinal Hormone - metabolism, genetics
- Metabolic Networks and Pathways - genetics
- Gastric Inhibitory Polypeptide - metabolism, genetics