This epigenetic imprinting is established perinatally and partially lost in glucose incompetent islets from diabetic mice and humans, which display increased expression of Fxyd3. Thus, gluco-incretin action early in life contributes to the establishment of the normal insulin secretion capacity of adult islets; loss of this imprinting may contribute to the pathogenesis of type 2 diabetes. Here, GCG is linked to type 2 diabetes mellitus.