Glucagon is a hormone produced by pancreatic alpha cells to maintain stable blood glucose levels, especially when they drop to low levels (Alpha cell).
Glucagon Sequence HSQGTFTSDYSKYLDSRRAQDFVQWLMNT.
Glucagon binds to a specific G-protein-coupled receptor (GCGR) located primarily on liver cells and kidney cells, activating adenylate cyclase, leading to elevated intracellular cyclic AMP (cAMP) and the activation of protein kinase A (PKA), which drives the metabolic enzymes required for glucose and fat breakdown.
When blood sugar decreases, glucagon signals the liver to release glucose through two main processes:
During glycogenolysis glucagon stimulates the liver to break down stored glycogen into glucose, which is then released into the bloodstream to raise blood sugar quickly. Glucagon triggers the liver to release stored glucose and produce new glucose, raising blood sugar levels. Glucagon reduces the liver's glucose consumption and stimulates fat breakdown, providing alternative energy sources, further supporting blood sugar levels.
During gluconeogenesis when glycogen stores are low, glucagon promotes the production of new glucose from non-carbohydrate sources such as amino acids and fats, providing a sustained energy supply.
Glucagon works together with insulin, which lowers blood glucose after meals, creating a feedback system that keeps blood sugar within a healthy range. However, unlike insulin, which lowers blood sugar, glucagon signals the liver to break down stored glycogen into glucose, rapidly releasing it into the bloodstream to raise blood glucose levels.
Glucagon is a 29-amino acid hormone used as a diagnostic aid in radiologic exams to temporarily inhibit the gastrointestinal tract's movement and treat severe hypoglycemia. Glucagon raises blood sugar by activating hepatic glucagon receptors, stimulating glycogenolysis and the release of glucose.
Common Brand Names are Baqsimi, a nasal powder, Gvoke, a pre-filled syringe or auto-injector, and GlucaGen / GlucaGon, a powder for injection.
Glucagon Physiology
The primary role of glucagon is to prevent hypoglycemia by stimulating hepatic glucose production via glycogenolysis and gluconeogenesis, and by promoting fat and amino acid metabolism to maintain whole-body energy homeostasis.
In the liver, glucagon stimulates the liver to break down stored glycogen into glucose (Glycogenolysis) and to synthesize new glucose from amino acids and other substrates (gluconeogenesis), rapidly increasing blood glucose to fuel the brain and other tissues.
Glucagon also promotes lipolysis, or fat breakdown, and fatty acid oxidation in the liver, while stimulating the production of ketones. Further, glucagon enhances hepatic amino acid uptake and drives ureagenesis by converting ammonia into urea, providing carbon skeletons for gluconeogenesis.
During fasting and after protein-rich meals, glucagon secretion increases. Hormones and neurotransmitters such as epinephrine also stimulate its release. Glucagon is inhibited by high blood sugar levels and by insulin, which acts directly on the alpha cells via the local islet microvasculature.
Reference
Baqsimi,
Baig MH, Ahmad K, Hasan Q, Khan MK, Rao NS, Kamal MA, Choi I. Interaction of Glucagon G-Protein Coupled Receptor with Known Natural Antidiabetic Compounds: Multiscoring In Silico Approach. Evid Based Complement Alternat Med. 2015;2015:497253. [PMC]
Drugbank
Gvoke HypoPen® (glucagon injection)
Physiology
Zeigerer A, Sekar R, Kleinert M, Nason S, Habegger KM, Müller TD. Glucagon's Metabolic Action in Health and Disease. Compr Physiol. 2021 Apr 1;11(2):1759-1783. [PMC]
“Bio-Synthesis is a business-to-business contract manufacturing and research organization. We do not sell GLP therapeutics directly to the public, dispense prescription medications, or provide medical treatment. This article is intended for scientific and industry discussion only and should not be interpreted as medical advice. Patients should consult licensed healthcare professionals regarding GLP-based therapies.”