Alloxan and streptozotocin are toxic glucose analogues that selectively accumulate in pancreatic beta cells via the GLUT2 glucose transporter. Alloxan generates reactive oxygen species (ROS) through a cyclic redox reaction with its reduction product, dialuric acid, leading to the death of beta cells. Streptozotocin, an alkylating agent, modifies biological macromolecules and damages DNA, causing beta cell destruction. Both compounds inhibit glucose-induced insulin secretion through different mechanisms: alloxan inhibits glucokinase, while streptozotocin alkylates DNA. The selective toxicity of these compounds is due to their ability to enter beta cells via the GLUT2 transporter. The generation of ROS and DNA alkylation mediate their toxic actions, respectively. Alloxan and streptozotocin induce insulin deficiency and beta cell necrosis, providing insights into the mechanisms of beta cell death in type 1 and type 2 diabetes.Alloxan and streptozotocin are toxic glucose analogues that selectively accumulate in pancreatic beta cells via the GLUT2 glucose transporter. Alloxan generates reactive oxygen species (ROS) through a cyclic redox reaction with its reduction product, dialuric acid, leading to the death of beta cells. Streptozotocin, an alkylating agent, modifies biological macromolecules and damages DNA, causing beta cell destruction. Both compounds inhibit glucose-induced insulin secretion through different mechanisms: alloxan inhibits glucokinase, while streptozotocin alkylates DNA. The selective toxicity of these compounds is due to their ability to enter beta cells via the GLUT2 transporter. The generation of ROS and DNA alkylation mediate their toxic actions, respectively. Alloxan and streptozotocin induce insulin deficiency and beta cell necrosis, providing insights into the mechanisms of beta cell death in type 1 and type 2 diabetes.