Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells

► Glycated serum (GS) induced apoptosis in pancreatic β-cells, inhibited the glucose stimulated insulin secretion (GSIS) function in rat islets. ► Treatment with GS increased the receptor for AGEs (RAGE) protein production in cultured pancreatic β-cells. ► GS treatment also decreased bcl-2 gene expression, followed by mitochondrial swelling, increased cytochrome c release, and caspase activation. ► RAGE antibody and knockdown of RAGE reversed the β-cell apoptosis and bcl-2 expression. ► Inhibition of RAGE reversed the insulin gene expression, but could not restore the GSIS function in rat islets.