Glucagon

**Glucagon** is a vital counter-regulatory polypeptide hormone naturally secreted by the alpha-2 cells of the pancreas. In veterinary medicine, it serves as a critical emergency and critical care drug. * **Primary Use**: Rapidly increases blood glucose levels in patients suffering from severe hypoglycemia, particularly due to **insulinoma** (endogenous insulin excess) or **insulin overdose** (exogenous excess). * **Large Animal Application**: Shows potential for treating **fatty liver syndrome (hepatic lipidosis)** in dairy cattle. * **Toxicology**: While used in human medicine for beta-blocker and calcium-channel blocker overdoses, veterinary studies (e.g., in dogs) suggest high-dose insulin therapy may be superior for propranolol toxicity. **Clinical Pearl**: Glucagon relies on adequate hepatic glycogen stores to be effective. In severely emaciated or cachectic patients with depleted glycogen, its efficacy may be significantly blunted.

กลไกการออกฤทธิ์: Glucagon acts as a physiological antagonist to insulin, primarily targeting the liver to increase blood glucose levels. * Binds to specific **glucagon receptors (GPCRs)** on the surface of hepatocytes. * Activates **adenylate cyclase** → increases intracellular **cAMP** → activates **protein kinase A (PKA)**. * This cascade stimulates **glycogen phosphorylase** and inhibits glycogen synthase, leading to rapid **hepatic glycogenolysis** (breakdown of stored glycogen into glucose) and **gluconeogenesis**. * Also causes relaxation of gastrointestinal smooth muscle through poorly understood mechanisms (likely cAMP-mediated).

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