Thanks for raising this question, if answered, may explain diversity of positive impact on health together with unexplained side effects
https://www.researchgate.net/publication/386339609_A_Revolutionary_Road_Map_for_Obesity_Management_and_Beyond_Tirzepatide_as_a_Dual-Acting_Insulinotropic_Polypeptide_Receptor_Agonist
Glucagon-like peptide-1 (GLP-1) primarily binds to the GLP-1 receptor (GLP-1R), which is a G-protein-coupled receptor involved in regulating insulin secretion, glucose metabolism, and appetite suppression. However, some studies suggest that GLP-1 may have interactions beyond GLP-1R, either directly or through cross-talk with other receptor systems:
1. Cross-Talk with Other Receptors: GLP-1's signaling effects can overlap with other receptors involved in metabolic pathways, such as the glucagon receptor (GCGR) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). This is particularly relevant in the context of dual agonists (e.g., GLP-1/GIP or GLP-1/glucagon receptor agonists), which are being developed for enhanced metabolic effects.
2. Binding to Other Sites in Pathological Contexts: In certain disease states, such as cancer or cardiovascular conditions, GLP-1 or its receptor agonists might influence other pathways indirectly, such as those mediated by growth factors or inflammatory signals.
3. Non-Canonical GLP-1 Effects: There is evidence of GLP-1 activity in tissues without high GLP-1R expression, suggesting potential receptor-independent effects, possibly mediated through interactions with different signaling proteins or receptors not yet fully characterized.
Thus, while GLP-1 primarily acts through GLP-1R, it may influence other receptors or systems indirectly or in specific physiological and pathological contexts. Further research is ongoing to fully map these interactions.
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