This discussion was a major theme at a European Association for the Study of Diabetes–sponsored symposium on glucagon recently held in Oxford, England (21st European Association for the Study of Diabetes Hagedorn Oxford Workshop: Glucagon, the Alpha Cell and Intraislet Paracrine Relationships; chairs: Jens Juul Holst and Patrik Rorsman, August 2016), with representatives from many of the groups that had been engaged in this debate and had carried out experimental work to understand these new observations. This evidence concerns the gene GCG and diabetes mellitus.