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Interestingly, despite the lack of metabolic consequence in hepatocyte RAMP2-overexpressing mice, hepatocyte-specific knockdown of the endosomal protein VPS37a within in vitro and ex vivo settings increases ligand-bound GcgR localization into G s accessible endosomes, enhances total G s /cAMP signaling, reduces lysosomal targeting, and alters endosomal localization which when applied in vivo significantly upregulates glucose production and biases hepatic metabolic flux away from fatty acid oxidation [164]

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The receptors adapt over weeks, and the side effects that scare people off almost always trace back to moving too fast rather than to the compounds themselves

SG, XF, GY, CC, SZ, and XL performed the experiments and analyses