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- W4386887016 abstract "Simultaneous activation of the incretin G protein coupled receptors via unimolecular dual-receptor agonists (UDRA) has emerged as a new therapeutic approach for type 2 diabetes. Recent studies also advocate triple agonism with molecules also capable of binding the glucagon receptor. In this scoping review we discuss the cellular mechanisms of action (MOA) underlying the actions of these novel and therapeutically important classes of peptide receptor agonists. Clinical efficacy studies of several UDRAs have demonstrated favourable results both as monotherapies and when combined with approved hypoglycaemics. While the additive insulinotropic effects of dual GLP-1R and GIPR agonism were anticipated based on the known actions of either GLP-1 or GIP alone, the additional benefits from GCGR were largely unexpected. Whether additional synergistic or antagonistic interactions among these G-protein receptor signalling pathways arise from simultaneous stimulation is not known. The signalling pathways affected by dual- and tri-agonism require more trenchant investigation before a comprehensive understanding of the cellular MOA. This knowledge will be essential for understanding the chronic efficacy and safety of these treatments." @default.
- W4386887016 created "2023-09-21" @default.
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- W4386887016 date "2023-09-20" @default.
- W4386887016 modified "2023-10-14" @default.
- W4386887016 title "Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets" @default.
- W4386887016 doi "https://doi.org/10.1152/ajpendo.00236.2023" @default.
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