The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions

► Hyperglycemia exert “toxic” effects on the β-cell phenotype in type 2 diabetes. ► β-Cell “glucotoxicity” involves complex cellular and molecular mechanisms. ► ROS, UPR and loss of differentiation play major roles in β-cell glucotoxicity. ► There is an emerging role of AGEs and hypoxia in β-cell glucotoxicity. ► Manipulation of these mechanisms is protective in vitro and in animal models.