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Glucagon

Glucagon is a 29-amino acid polypeptide acting as an important hormone in carbohydrate metabolism. The polypeptide has a molecular weight of 3485 daltons and was discovered in 1923 by Kimball and Murlin. more...

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Its primary structure is: NH₂-His-Ser-Gln-Gly-Thr-Phe- Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser- Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH

History

In the 1920s, Kimball and Murlin studied pancreatic extracts and found an additional substance with hyperglycemic properties. Glucagon was sequenced in the late-1950s, but a more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed.

Physiology

The hormone is synthesized and secreted from alpha cells of the Islets of Langerhans, which are located in the pancreas. The alpha cells are located in the outer rim of the islet.

Regulation

Stimulus for increased secretion of glucagon

Decreased plasma glucose
Increased catecholamines
Increased plasma amino acids (to protect from hypoglycemia if an all protein meal consumed)
Sympathetic nervous system

Stimulus for decreased secretion of glucagon

Somatostatin
Insulin

Function

Glucagon helps maintain the level of glucose in the blood by binding to specific receptors on hepatocytes, causing the liver to release glucose - stored in the form of glycogen - through a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of hypoglycemia.

Increased free fatty acids and ketoacids into the blood
Increased urea production

Mechanism of action

Acts via cAMP generation

Pathology

Abnormally-elevated levels of glucagon may be caused by pancreatic cancers such as glucagonoma, symptoms of which include necrolytic migratory erythema (NME).

Pharmacological application of glucagon

An injectable form of glucagon is essential first aid in cases of severe hypoglycemia. The glucagon is given by intramuscular injection, and quickly raises blood glucose levels. It works only if there is glycogen stored in liver cells, and it won't work again until those stores are replenished.

Glucagon has also inotropic properties. Although its use is impracticable in heart failure, it has some value in treatment of myocardial depression secondary to betablocker overdose. However there have been no clinical controlled trial on the use of glucagon.

Media

Read more at Wikipedia.org

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GlucaGen® HypoKit : an important consideration for all patients treated with insulin - glucagon rys
From Diabetes and Primary Care, 6/22/02

Many patients treated with insulin will experience severe hypoglycaemia at some time; yet relatively few have glucagon on hand. This is despite the fact that severe hypoglycaemia is considered to be a major cause of anxiety amongst insulin-treated patients. (1)

Causes of hypoglycaemia include skipping meals, stress, taking too much exercise or drinking too much alcohol. However, perhaps a more troubling cause is linked to intensive insulin therapy.

The risk of a severe hypoglycaemic event is 2-3 times higher in patients aiming to achieve optimal glucose control with intensive insulin therapy. (2) The fear of hypoglycaemia may inhibit patients from maintaining tight control of their blood sugar, thus depriving them of the key benefits intensive control offers, i.e. significant delay or prevention of long-term complications.

Healthcare professionals dealing with diabetes patients on a regular basis will be well attuned to the fear their patients have about hypoglycaemia. It is therefore important that glucagon administration is included as part of patient education programmes. Glucagon should be considered as a way of helping patients overcome their anxiety surrounding hypoglycaemia and become as expert as possible in achieving optimal control over their diabetes. Healthcare professionals can play a key role in ensuring that all patients and their relatives receive adequate training on hypoglycaemia and the use of glucagon.

The Novo Nordisk GlucaGen HypoKit provides a user friendly means of administering glucagon. For further information please call the Novo Nordisk Customer Care Line 0845 600 5055. (calls are charged at local rates and may be monitored for training purposes)

(1.) Pramming S. Thorsteinsson B. Bendtson I. Binder C. Diab Med 1991, 8: 217-222

(2.) DCCT Research Group. N Engl J Med 1993, 329: 977-86

(Prescribing information for GlucaGen HypoKit is on p. 3)

RELATED ARTICLE: ABBREVIATED PRESCRIBING INFORMATION FOR GLUCAGEN HYPOKIT 1MG

GlucaGen HypoKit 1mg Glucagon (rys)

Presentation: A vial containing 1mg (1 iu) glucagon (rys), as the hydrochloride, and lactose 107mg, together with a pre-filled syringe containing 1 ml Water for injections.

Uses: The treatment of severe hypoglycaemic reactions which may occur in the management of diabetic patients receiving insulin. As a motility inhibitor in examinations of the gastrointestinal tract. As a motility inhibitor in CT, NMR and DSA.

Dosage: The glucagon is dissolved in the accompanying diluent before use.

Treatment of severe hypoglycaemic reactions: 1mg (adults, children above 25kg or 6 - 8 years) or 0.5mg (children below 25kg or 6 - 8 years) by subcutaneous, intramuscular, or intravenous injection. When the patient responds, administer oral carbohydrate. If no response within 10 minutes, give intravenous glucose.

Diagnostic indications: Doses range from 0.1-2mg depending on the diagnostic technique used and the rank of administration. Usual dose for relaxation of stomach. duodenal bulb, duodenum and small bowel is 0.2-0.5mg i.v. or 1mg i.m. To relax the colon 0.5-0.75mg iv. or 2mg i.m. In CT, NMR and OSA doses up to 1mg i.v. are used.

Contra-indications: Phaeochromocytoma. Hypersensitivity to glucagon or excipients. Do not use if solution contains particles, or has viscous appearance.

Precautions: Glucagon reacts antagonistically towards insulin. Observe caution in patients with insulinoma or glucagonoma, and in diabetics or elderly patients with known cardiovascular disease.

Use in pregnancy: Glucagon does not cross the placenta. Glucagon has been used in pregnant diabetics; no harmful effects known with respect to course of pregnancy or health of foetus and neonate.

Side effects: Occasionally nausea and vomiting, which tends to be dose related. Positive inotropic and chronotropic effects (tachycardia). Rarely hypersensitivity.

PL numbers: GlucaGen 1mg PL 4668/0027

Diluent for GlucaGen 1mg fsyhnge) PL 4666/0026

Legal category: POM

Basic NHS price: GlucaGen HypoKit 1mg [pounds sterling]19.95 Full prescribing information can be obtained from: Novo Nordisk Limited, Broadfield Park, Brighton Road, Crawley, West Sussex RH 11 9RT. Tel: (01293) 613555

Date of Preparation: May 2002

HOW TO ADMINISTER GLUCAGEN: A STEP-BY-STEP GUIDE

1. Insert the needle through the rubber disk of the GlucaGen bottle and inject all of the contents of the syringe into the bottle.

2. Without withdrawing the syringe, gently shake the bottle until the GlucGen is completely dissolved.

3. Ensure that the plunger is first fully depressed. Then draw up the entire solution into the syringe.

4. Ensure there is no air remaining in the syringe before giving the injection. When the patient responds, give them a sweet drink or snack to prevent a further hypo.

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