Hormones are compounds secreted by specific tissues called endocrine glands (Figure 23.6). Endocrine glands secrete hormones directly into the bloodstream, so the response to a hormonal signal comes as a direct and rapid result of its secretion. Glucagon is a 3.5-kilodalton polypeptide hormone synthesized by the A cells of the islets of Langerhans in the pancreas. These endocrine cells sense the blood glucose concentration and release glucagon in response to low levels (see Figure 23.2 and Table 23.1). Both synthesis and release of glucagon are controlled by insulin.

In the liver, glucagon increases cyclic AMP (cAMP) levels, as schematized in Figure 23.3. The resultant metabolic cascades, discussed in Chapters 13 (here) and 16 (here), promote glycogenolysis and inhibit glycogen synthesis. In addition, by activating the hydrolysis of fructose-2,6-bisphosphate, cAMP inhibits glycolysis and activates gluconeogenesis (see here).

Glucagon brings about the inhibition of pyruvate kinase (PK) in the liver, causing phosphoenolpyruvate (PEP) to accumulate. The level of pyruvate decreases, both because its synthesis from PEP is blocked and because it continues to be converted to PEP, via the pyruvate carboxylase and phosphoenolpyruvate carboxykinase reactions. Accumulation of PEP promotes gluconeogenesis, while the inhibition of pyruvate kinase diminishes the glycolytic flux rate.

Glucagon also raises cAMP levels in adipose tissue. There the chief effect of cAMP is to promote triacylglycerol mobilization via phosphorylation of hormone-sensitive lipase, yielding glycerol and fatty acids.