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 β-cells that is partially lost in individuals affected by Type 2 diabetes. This unique property of β-cells is acquired through a poorly understood postnatal maturation process involving major modifications in gene expression programs. Here we show that β-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 β-cell maturation and in the determination of adult functional β-cell mass. A better understanding of the events governing β-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.
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland.
Cécile
C
Jacovetti
Department of Internal Medicine, Center for Pharmacogenomics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Scot J
SJ
Matkovich
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland.
Adriana
A
Rodriguez-Trejo
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland.
Claudiane
C
Guay
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland.
Romano
R
Regazzi
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014886:Weaning
D007328:Insulin; D035683:MicroRNAs