An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

Figure 1

Beneficial effects of GLP-1 in pancreatic beta cells exposed to AGEs. The activation of the AGEs-RAGE axis in pancreatic beta cells increases oxidative stress that causes mitochondrial dysfunction, endoplasmic reticulum stress, and altered signal transduction. These detrimental effects modify gene expression leading to increased expression of RAGE and proapoptotic molecules, and downregulation of proteins involved in insulin gene expression, such as PDX-1, thus causing decreased insulin production and loss of glucose-stimulated insulin secretion (GSIS). Activation of GLP-1 signaling increases antioxidant defense thus counteracting formation of reactive oxygen species (ROS) and expression of RAGE, blocking the positive feedback loop that links RAGE activation with RAGE expression. Furthermore, GLP-1 maintaining pancreatic beta-cell function restores GSIS, thus contributing to reduce plasma glucose concentration and, consequently, formation of new AGEs.