Different pathways of insulin secretion, links between them and effects of simvastatin on these pathways.

<p>Simvastatin (Simva) decreases insulin secretion mediated by ATP-sensitive potassium (K_ATP) channels (A), membrane depolarization and voltage-gated calcium channels (B), and acetylcholine and GPR40 receptors (C and D). These effects may be attributable to simvastatin´s actions on K_ATP channels, calcium channels, or Ca²⁺ release from endoplasmic reticulum <i>via</i> inositol 3-phophate (IP3) and ryanodine receptors (RYR). Activation of GLP-1R (E) and GPR119 (F) pathway restores simvastatin-decreased insulin secretion. DAG—diacylglycerol, EPAC2—exchange protein activated by cAMP 2, ER—endoplasmic reticulum, Inos(1,4,5)P₃ –inositol 1,4,5-triphosphate, PKA—protein kinase A, PLCβ–phospholipase C beta, PtdInos(4,5)P_2—phosphatidylinositol 4,5-bisphosphate.