Our aim was to investigate, using mathematical modelling, the role of alpha cell dysregulation in beta cell compensatory insulin secretion and subsequent failure in the progression from normoglycaemia to type 2 diabetes defined by ADA criteria.<h4>Methods</h4>We developed a physiological model of glucose homeostasis, whereby the fast dynamics of glucose, insulin and glucagon are coupled to the dynamics of beta cell functional mass (a product of individual beta cell functional capacity and mass). This evidence concerns the gene GCG and type 2 diabetes mellitus.