Figure 2  Inhibitory effects of nitric oxide (NO) on insulin secretion. Glucose that enters the β‐cells via glucose transporter type 2 (GLUT-2) is phosphorylated by glucokinase and its metabolism through Krebs cycle, increases cytoplasmic adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio. An increased ATP/ADP ratio closes ATP‐sensitive K+ channels (KATP channels) and causes membrane depolarization and the subsequent activation of L‐type voltage‐dependent Ca2+ channels (VDCC); elevation of cytosolic Ca2+ level leads to insulin vesicles exocytosis. Nitric oxide by formation of ironnitrosyl complexes with FeS-containing enzymes causes reversible inactivation of the mitochondrial enzyme aconitase; NO also reacts with a number of sulfhydryl-containing proteins; functionally essential SH groups in glucose binding site of glucokinase is a target for oxidizing agents. Furthermore, NO increases K+ outflow from the β-cells and therefore decreases Ca2+ entry through VDCC which inhibits insulin secretion.