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Glucagon
promote
1)glycogenolysis
2)gluconeogenesis
3)fatty acid oxidation
4)ketogenesis
5)uptake of amino acids
inhibit
1)glycogenesis
function of both glucagon and epinephrine
1)glycogenolysis
2)gluconeogenesis
3)fatty acid oxidation
Epinephrine
promote
1)glycogenolysis
2)lipolysis
inhibit
1)insulin secretion
4)ketogenesis
5)uptake of amino acids
Humans have two overlapping glucose-regulating systems that are activated by hypoglycemia: 1) the
pancreatic α cells, which release glucagon, and 2) receptors in the hypothalamus, which respond to
abnormally low concentrations of blood glucose. The hypothalamic glucoreceptors can trigger both
the secretion of catecholamines (mediated by the sympathetic division of the autonomic nervous
system) and release of adrenocorticotropic hormone (ACTH) and growth hormone by the anterior
pituitary (see Fig. 23.13). [Note: ACTH increases cortisol synthesis and secretion in the adrenal cortex
(see p. 239).] Glucagon, the catecholamines, cortisol, and growth hormone are sometimes called the
counterregulatory hormones because each opposes the action of insulin on glucose use. 1. Glucagon
and epinephrine: Secretion of these counterregulatory hormones is most important in the acute,
short-term regulation of blood glucose levels. Glucagon stimulates hepatic glycogenolysis and
gluconeogenesis. Epinephrine promotes glycogenolysis and lipolysis. It inhibits insulin secretion,
thereby preventing GLUT-4–mediated uptake of glucose by muscle and adipose tissues. Epinephrine
assumes a critical role in hypoglycemia when glucagon secretion is deficient, for example, in the late
stages of type 1 diabetes mellitus (see p. 340). The prevention or correction of hypoglycemia fails
when the secretion of both glucagon and epinephrine is deficient. 2. Cortisol and growth hormone:
These counterregulatory hormones are less important in the short-term maintenance of blood
glucose concentrations. They do, however, play a role in the long-term (transcriptional)
management of glucose metabolism
The alpha pancreatic cells
Glucagon binds to high-affinity G protein–coupled receptors (GPCR) on the cell membrane of
hepatocytes. Glucagon binding results in activation of adenylyl cyclase in the plasma membrane. This
causes a rise in cyclic AMP (cAMP), which, in turn, activates cAMP-dependent protein kinase A and
increases the phosphorylation of specific enzymes or other proteins. This cascade of increasing
enzymic activities results in the phosphorylation-mediated activation or inhibition of key regulatory
enzymes involved in carbohydrate and lipid metabolism. An example of such a cascade in glycogen
degradation is shown in Figure 11.9 on p. 131. [Note: Glucagon, like insulin, affects gene
transcription. For example, glucagon induces expression of phosphoenolpyruvate carboxykinase (see
p. 122).]