page_title: Sulfonylurea
section_title: Mechanism of action
hierarchical_section_title: Sulfonylurea / Mechanism of action
context_page_description: Sulfonylureas are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas. A number of sulfonylureas are also used as herbicides, because they can interfere with plant biosynthesis of certain amino acids. Sulfonylureas are also used experimentally to inhibit interleukin 1 beta release from the NALP3 inflammasome.
context_section_description: Sulfonylureas bind to and close ATP-sensitive K⁺ (KATP) channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca²⁺ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of mature insulin.
  There is some evidence that sulfonylureas also sensitize β-cells to glucose, that they limit glucose production in the liver, that they decrease lipolysis (breakdown and release of fatty acids by adipose tissue) and decrease clearance of insulin by the liver.
  The KATP channel is an octameric complex of the inward-rectifier potassium ion channel Kᵢᵣ6.x and sulfonylurea receptor SUR which associate with a stoichiometry of 4:4.
  Furthermore, it has been shown that sulfonylureas interact with the nucleotide exchange factor Epac2. Mice lacking this factor exhibited a decreased glucose-lowering effect upon sulfonylurea treatment.
caption: Diagram of glucose reduction and insulin release in the pancreas