Glucagon secretion is increased during fasting. Which cell type in the islets of Langerhans secretes glucagon, and what is its primary receptor signalling cascade in hepatocytes?
- A Beta cells; glucagon receptor → Gq → ↑IP3 → Ca2+-calmodulin → phosphorylase kinase activation
- B Delta cells; glucagon receptor → Gi → ↓cAMP → dephosphorylation of glycogen synthase → glycogenesis
- C Alpha cells; glucagon receptor → JAK-STAT pathway → transcriptional upregulation of glucokinase
- D Alpha cells; glucagon receptor → Gs → ↑cAMP → PKA → phosphorylates glycogen phosphorylase kinase (activating glycogenolysis) and phosphorylates PFK-2 (inhibiting glycolysis/activating gluconeogenesis) ✓
Explanation
Glucagon is secreted by alpha cells of the islets of Langerhans during fasting/hypoglycaemia. In hepatocytes, glucagon binds its GPCR (glucagon receptor) coupled to Gs → adenylyl cyclase → ↑cAMP → PKA. PKA phosphorylates: (1) phosphorylase kinase (activating it, which activates glycogen phosphorylase b → a, driving glycogenolysis); (2) glycogen synthase (inactivating it, stopping glycogenesis); and (3) PFK-2 (inhibiting it, lowering fructose-2,6-bisphosphate, which relieves inhibition of FBPase-2 and inhibits PFK-1, thus inhibiting glycolysis and promoting gluconeogenesis). Net effect: rapid glucose output from the liver.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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