Glucagon

Glucagon is a peptide hormone involved in increasing blood levels of glucose.

1. Glucagon acts to stimulate production of cAMP inside of cells. It does this by binding to a specific receptor that, via interaction with a cell membrane G protein, stimulates the activity of the enzyme responsible for making cAMP, adenylate cyclase. cAMP acts as a "second messenger," conveying the signal from outside the cell to the inside and initiating the cell's response. Pathways affected by cAMP include glycogen metabolism, glycolysis, fatty acid biosynthesis.

2. Glucagon stimulates transcription of the enzyme phosphoenolpyruvate carboxykinase (PEPCK). PEPCK is a key enzyme in gluconeogenesis and transcription is the primary means of regulating it. By stimulating PEPCK transcription, glucagon can favor gluconeogenesis over glycolysis. (Conversely, the hormone insulin, which decreases blood glucose levels, stimulates PEPCK transcription.)

3. Glucagon represses synthesis of pyruvate kinase, the last enzyme in the glycolytic pathway. This to has the effect of favoring gluconeogenesis over glycolysis.

Note that transcription regulation mechanisms are relatively long-term effects (hours to days). When glucose levels need to be increased rapidly (in an emergency, for example), other mechanisms, such as stimulation of glycogen breakdown, must be employed. In this regard, glucagon differs from epinephrine. Both glucagon and epinephrine act to stimulate production of cAMP which stimulates glucose production, but epinephrine has no long term effects, as does glucagon.

See also: Kinase Cascade, Action of Glucagon, Phosphoenolpyruvate, Glycolysis, Pyruvate Kinase, Epinephrine