page_title: Glucagon (medication)
section_title: Mechanism of action
hierarchical_section_title: Glucagon (medication) / Mechanism of action
caption_attribution_description: English: Glucagon metabolic pathway to activate glycogen العربية: مسار التمثيل الغذائي الجلوكاجون لتنشيط الجليكوجين.
context_page_description: Glucagon is a medication and hormone. As a medication it is used to treat low blood sugar, beta blocker overdose, calcium channel blocker overdose, and those with anaphylaxis who do not improve with epinephrine. It is given by injection into a vein, muscle, or under the skin. A version given in the nose is also available.
  Common side effects include vomiting. Other side effects include low blood potassium and low blood pressure. It is not recommended in people who have a pheochromocytoma or insulinoma. Use in pregnancy has not be found to be harmful to the baby. Glucagon is in the glycogenolytic family of medications. It works by causing the liver to break down glycogen into glucose.
  Glucagon was approved for medical use in the United States in 1960. It is on the World Health Organization's List of Essential Medicines. It is a manufactured form of the glucagon hormone.
context_section_description: Glucagon binds to the glucagon receptor, a G protein-coupled receptor, located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. When the G protein interacts with the receptor, it undergoes a conformational change that results in the replacement of the GDP molecule that was bound to the α subunit with a GTP molecule. This substitution results in the releasing of the α subunit from the β and γ subunits.  The alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.
  Adenylate cyclase manufactures cyclic adenosine monophosphate (cyclic AMP or cAMP), which activates protein kinase A (cAMP-dependent protein kinase). This enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen phosphorylase b, converting it into the active form called phosphorylase a. Phosphorylase a is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers.
  Additionally, the coordinated control of glycolysis and gluconeogenesis in the liver is adjusted by the phosphorylation state of the enzymes that catalyze the formation of a potent activator of glycolysis called fructose-2,6-bisphosphate. The enzyme protein kinase A that was stimulated by the cascade initiated by glucagon will also phosphorylate a single serine residue of the bifunctional polypeptide chain containing both the enzymes fructose-2,6-bisphosphatase and phosphofructokinase-2. This covalent phosphorylation initiated by glucagon activates the former and inhibits the latter. This regulates the reaction catalyzing fructose-2,6-bisphosphate (a potent activator of phosphofructokinase-1, the enzyme that is the primary regulatory step of glycolysis) by slowing the rate of its formation, thereby inhibiting the flux of the glycolysis pathway and allowing gluconeogenesis to predominate. This process is reversible in the absence of glucagon (and thus, the presence of insulin).
  Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase.
caption: Metabolic regulation of glycogen by glucagon.
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