Although limiting due to the sparse availability of tissue, recent studies using isolated T1D donor islets and pancreatic slices have shown alpha-cells to lack an appropriate increase in [Ca2+]i and glucagon secretion in the presence of low glucose despite showing no difference in glucagon content when compared to non-diabetic donor islets/slices [242,243], suggesting that the mechanism(s) contributing to this glucagon secretory defect resides within the islets. This evidence concerns the gene GCG and type 1 diabetes mellitus.