Which hormone predominantly stimulates hepatic glycogenolysis during fasting?

• A. Insulin
• B. Epinephrine
• C. Glucagon
• D. Cortisol

Answer: (C)

During fasting the liver must maintain blood glucose, and glucagon is the key signal that triggers this. Released from pancreatic alpha cells when blood glucose falls, glucagon raises hepatic cAMP levels, which activates protein kinase A. This cascade activates glycogen phosphorylase and inhibits glycogen synthase, driving glycogenolysis to release glucose into the bloodstream. That’s why glucagon is the main hormonal driver of hepatic glycogen breakdown in the fasting state.

Insulin would oppose this process by promoting glycogen synthesis and glucose uptake, so it’s not driving glycogenolysis. Cortisol mainly supports gluconeogenesis and helps sustain glucose later in prolonged fasting, rather than the rapid glycogen breakdown. Epinephrine can stimulate glycogenolysis, especially under stress or exercise, but in a typical fasting situation glucagon provides the predominant regulatory signal for hepatic glycogenolysis.