Inhibition of Gcgr expression by Gcgr antisense oligonucleotides, abolishing glucagon production by deletion of prohormone convertase 2 gene or preproglucagon gene, small-molecule GCGR antagonists, GCGR-antagonizing antibodies, and liver-specific deletion of Gsα all result in α cell hyperplasia as seen in the Gcgr−/− mice and the patient with Mahvash disease [10]–[16], [18]–[20], [35]–[37]. Here, GNAS is linked to GCGR-related hyperglucagonemia.