What are the metabolic actions of glucagon?

Updated: Nov 13, 2018
  • Author: Cory Wilczynski, MD; Chief Editor: Eric B Staros, MD  more...
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Answer

Answer

Glucagon promotes energy storage in different types of tissues in response to feeding. The liver represents the major target organ for glucagon. The result of this can be seen in Table 2. Glucagon signaling occurs by way of glucagon receptors located on the surface of hepatocytes. Binding of glucagon and its receptor activates adenylyl cyclase and results in the generation of cyclic adenosine monophosphate (cAMP). Release of available energy stores from the liver—in the form of glucose (gluconeogenesis) and ketones (ketogenesis)—occurs via the glucagon signaling pathway. [1]

In cardiac tissue, glucagon has a potent inotropic and chronotropic effect mediated by cAMP. In the small intestine, glucagon has been known to relax smooth muscle in large amounts. [7]

Different amino acids have different effects on glucagon. Arginine promotes the release of both glucagon and insulin. Alanine mainly stimulates glucagon release. Leucine stimulates the release of insulin but not glucagon. Other substances like catecholamines, gastrointestinal hormones, gastrin, gastric inhibitory polypeptide, and glucocorticoids stimulate glucagon release. Glucagon secretion is suppressed by high fatty acid levels. [1]

The most important clinical use of glucagon is as a drug that, in its recombinant form, is employed to treat severe hypoglycemic reactions in diabetic patients. A glucagon pen, or GlucaPen, contains 1 mg of the recombinant hormone that should be injected intramuscularly when oral feedings are not possible or patients are completely unresponsive. Glucagon is also sometimes useful for reversing the cardiac effects of a beta-blocker overdose. [7]

Table 2: Metabolic Actions of Insulin and Glucagon  [3]

Table. (Open Table in a new window)

Fatty acid uptake and release in fat

Insulin

Stimulates synthesis of triglycerides (TG) from free fatty acids (FFA); inhibits release of FFA from TG .

Glucagon

Stimulates release of FFA from TG.

Liver glycogen

Insulin

Increases synthesis and thereby glucose uptake and storage.

Glucagon

Stimulates glycogenolysis and glucose release.

Liver gluconeogenesis

Insulin

Inhibits, saves amino acids.

Glucagon

Stimulates, glucose synthesized and released.

Glucose uptake, skeletal muscle

Insulin

Stimulates uptake, storage as glycogen and use in energy metabolism.

Glucagon

No receptors, no effect.

Glycogen, skeletal muscle

Insulin

Stimulates synthesis.

Glucagon

No receptors, no effect.

Amino acid uptake

Insulin

Stimulates and is necessary for protein synthesis.

Glucagon

No receptors, no effect.

Brain (hypothalamus)

Insulin

Reduces hunger through hypothalamic regulation.

Glucagon

No effect.


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