Gestational diabetes mellitus (GDM) is often accompanied by the development of hyperinsulinemia as an adaptation to increased insulin demand, but this subsequently causes insulin resistance. Loss of function in pancreatic beta-cells further aggravates the development of GDM. The level of serum platelet-derived growth factor (PDGF) reportedly increases in GDM patients. The present study investigated whether enhanced PDGF signaling directly causes beta-cell dysfunction during gestation. Serum PDGF levels were negatively correlated with beta-cell function in GDM patients. Administration of PDGF-BB disrupted glucose tolerance and beta-cell function without inducing apoptosis in gestational mice but had no similar effect in non-gestational mice. The beta-cell-specific genes encoding insulin synthesis proteins were decreased in the islets of PDGF-BB-treated gestational mice. In vitro experiments using INS1 insulinoma cells showed that PDGF-BB promoted cell proliferation, whereas it downregulated beta-cell-specific genes. Taken together, these findings suggested that PDGF reduces beta-cell function during gestation possibly through beta-cell dedifferentiation. (C) 2019 Elsevier Inc. All rights reserved.