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Orforglipron, instead, binds within a defined transmembrane receptor pocket, enabling oral bioavailability in experimental systems

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The ENS also expresses GLP-1 receptors 39 , but the local effects of GLP-1 could not be proven because GLP-1RA was ineffective in our studies in Ussing chamber experiments

We propose that hepatic activation of TH signaling has insulinotropic and glucose-lowering effects, as it is able to increase non-12-OH FXR-antagonistic BA levels through shaping the BA composition by repressing hepatic CYP8B1, thereby enhancing the GLP-1 production via suppressing intestinal FXR signaling

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