Physiology · Endocrine Physiology (Pituitary, Thyroid, Adrenal, Pancreas)

In a patient with a glucagonoma, which metabolic consequence is MOST directly attributable to chronic glucagon excess?

  • A Hypoglycaemia from insulin counter-regulatory failure
  • B Hyperglycaemia from stimulation of hepatic glycogenolysis and gluconeogenesis
  • C Metabolic acidosis from glucagon-stimulated fatty acid synthesis
  • D Hypokalaemia from glucagon-stimulated renal K+ excretion
Correct answer: B. Hyperglycaemia from stimulation of hepatic glycogenolysis and gluconeogenesis

Explanation

Glucagon acts on Gs-coupled glucagon receptors in hepatocytes, raising cAMP and activating PKA, which phosphorylates glycogen phosphorylase (activating it) and glycogen synthase (inactivating it). Simultaneously, glucagon upregulates gluconeogenic enzymes (PEPCK, FBP-1) and inhibits pyruvate kinase. Net result is increased hepatic glucose output causing hyperglycaemia — the defining metabolic feature of glucagonoma along with the 4 D's (diabetes, dermatitis, deep vein thrombosis, depression). Glucagonoma characteristically causes diabetes mellitus, NOT hypoglycaemia.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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