Which hormone stimulates liver glycogenolysis during low blood sugar?

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When blood sugar drops, a rapid signal is sent to the liver to release stored glucose. The hormone that does this most directly is glucagon, released by pancreatic alpha cells in response to low glucose. Glucagon binds to receptors on liver cells and raises cyclic AMP, which activates the enzyme glycogen phosphorylase. That enzyme breaks down glycogen into glucose-1-phosphate and then free glucose, which is released into the bloodstream to raise blood sugar quickly. At the same time, enzymes for building glycogen are inhibited, helping prioritize glucose release over storage.

Insulin does the opposite, promoting glycogen synthesis and lowering blood glucose, so it wouldn’t stimulate glycogenolysis. Epinephrine can also drive glycogen breakdown, especially during stress or exercise, but its role is not the primary response to hypoglycemia. Cortisol supports glucose availability over a longer period by promoting gluconeogenesis rather than immediate glycogenolysis.