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long-term safety unknown Glucagon Glucagon, a peptide, produced by A cells of the pancreatic islets of Langerhans Glucagon is arrived from a large precursor peptide (one intermediate: glicentin, 69-amino acid peptide) Rapidly inactivated in plasma (degraded also at hepatic, renal, and tissue receptor sites) Enteroglucagons: Glicentin immunoreactivity: cells of the small intestine, pancreatic A cells, pancreatic effluent-- glucagon-like peptides Glucagon: Pharmacological activity Metabolic: glucagon interacts with specific, hepatic receptors G protein activation, increase in adenylyl cyclase activity, increases cAMP production Increased catabolism of stored glycogen, increased gluconeogenesis, increased ketogenesis Pharmacological consequences: increased blood glucose, decreased hepatic glycogen insulin released from normal pancreatic B cells catecholamines from pheochromocytoma calcitonin from medullary carcinoma Cardiovascular Effects: positive inotropic action (increased myocardial contractility) positive chronotropic (increased heart rate) these effects mediated by cAMP Smooth Muscle Effects: (large doses): intestinal smooth muscle relaxation Management of Severe Hypoglycemic States emergency treatment in insulin-dependent unconscious patients in which intravenous glucose cannot be administered (a conscious patient would be treated by drinking orange juice or other high sugar content foods) Glucagon is available for parenteral use

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