Postnatal β-cell maturation is associated with islet-specific microRNA changes induced by nutrient shifts at weaning

Glucose-induced insulin secretion is an essential function of pancreatic beta-cells that is partially lost in individuals affected by Type 2 diabetes. This unique property of beta-cells is acquired through a poorly understood postnatal maturation process involving major modifications in gene expression programs. Here we show that beta-cell maturation is associated with changes in microRNA expression induced by the nutritional transition that occurs at weaning. When mimicked in newborn islet cells, modifications in the level of specific microRNAs result in a switch in the expression of metabolic enzymes and cause the acquisition of glucose-induced insulin release. Our data suggest microRNAs have a central role in postnatal beta-cell maturation and in the determination of adult functional beta-cell mass. A better understanding of the events governing beta-cell maturation may help understand why some individuals are predisposed to developing diabetes and could lead to new strategies for the treatment of this common metabolic disease.