Glucagon

Original Author: Neil Thakrar
Last Updated: 22nd December 2017
Revisions: 10

Glucagon is the hormone that opposes insulin, so it acts to raise blood glucose levels. It is a peptide hormone, produced by the alpha cells of the pancreas.

This article shall consider the structure of glucagon, its synthesis, secretion, mechanism of action and clinical conditions that may result from faults in this process.

Structure

Glucagon is a single chain polypeptide and has no disulfide bridges, making it flexible.

Fig 1 – Representation of the structure of glucagon.

Synthesis

A precursor molecule, proglucagon, undergoes post-translational processing to become a biologically active glucagon.

Secretion

Glucagon is secreted by alpha cells in the islets of Langerhans in the tail of the pancreas. Low glucose levels in the blood are detected by alpha cells, stimulating the release of glucagon. Like insulin, this undergoes margination and exocytosis to be released.

Mechanism of Action

Glucagon binds to a specific glucagon receptor in the cell membrane, a G Protein Coupled Receptor (GPCR). This activates the enzyme adenylate cyclase which increases cAMP intracellularly. This activates protein kinase A which phosphorylates and activates a number of important enzymes in target cells.

Overall effects

The overall metabolic effects of glucagonĀ are typically exerted on the liver:

  • Increased glycogenolysis
  • Decreased glycogenesis
  • Increased gluconeogenesis
  • Increased ketogenesis

It also increases lipolysis in adipose tissue

Control of Glucagon

Stimulates Glucagon Secretion Inhibits Secretion
Adrenaline GI tract hormones
Noradrenaline Acetylcholine

Clinical Relevance – Glucagonoma

A glucagonoma is a tumour of the alpha cells of the pancreas. These tumours lead to the overproduction of glucagon, which can cause a variety of symptoms:

  • Hyperglycaemia
  • Weight loss
  • Anaemia
  • Diarrhoea
  • Diabetes mellitus

The presenting problem in most cases however, is Necrolytic Migratory Erythema (NME), a red, blistering rash that spreads across the skin. It particularly affects the skin around the mouth and extremities, but can also be found on the lower abdomen, perineum and groin.

A blood serum glucagon of more than 1000pg/mL is indicative of a glucagonoma and the tumour can be localised using radiography such as CT or MRI scans.

Medication that inhibits glucagon release or damages alpha cells in the pancreas can be used to help minimize symptom progression, however the only curative treatment is surgical resection of the tumour.

Quiz

Question 1 / 5
How many inter-chain disulphide bridges are there in a mature glucagon molecule?

Quiz

Question 2 / 5
Which cell type in the Islets of Langerhans secrete glucagon?

Quiz

Question 3 / 5
Which of the following is NOT an effect of glucagon?

Quiz

Question 4 / 5
Which of the following statements is TRUE?

Quiz

Question 5 / 5
Which of the following blood glucagon concentrations would indicate a glucagonoma?

Results

Rate This Article

2

Average Rating: