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reported that Gcg / mice with selective re-expression of intestinal proglucagon did not exhibit glucose intolerance in response to treatment with the GLP-1R antagonist, Exendin 9-39, whereas mice with selective re-expression of pancreatic proglucagon did exhibit glucose intolerance in response to Exendin 9-39 ( Gcg / mice with selective re-expression of Gcg in the pancreas or the gut revealed a role for pancreatic, but not intestinal, proglucagon products, in the metabolic benefits of vertical sleeve gastrectomy (VSG) ( Indeed, this limitation is increasingly relevant in light of evidence that the insulinotropic effects of glucagon are predominantly mediated by the GLP-1R ( Figure 2 )

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