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Protective MC4R variants identified in the UK Biobank exhibited signaling bias toward -arrestin recruitment and increased MAPK pathway activation suggesting that -arrestin-biased MC4R signaling may represent an effective strategy for weight loss (109, 110)

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However, a DPPIV inhibitor retained its glucose lowering effects in these mice, suggesting that the GLP-1R on the beta cell is not necessary for these effects, and that perhaps extra-islet receptors are responsible for the incretin effects of GLP-1