Glucagon and hyperglycemic agents
The regulation of glycemia, taking into account the discontinuous food intake and the variable requirements of the body, requires complex mechanisms and glucagon takes part by effects oppositing those of insulin.
Glucagon is an hyperglycemic polypeptic hormone secreted by alpha cells of the pancreas and intestinal tract, discovered little time after insulin.
Metabolism
Glucagon consists of a single-chain of 29 amino acid residues. Its secretion is inhibited by glucose and somatostatin and is stimulated by amino acids. Its plasma half-life is a few minutes because it is hydrolyzed in many tissues, particularly the liver.
An excessive glucagon secretion is observed in certain diabetics.
Effects
Glucagon stimulates receptors coupled to Gs proteins and activation of adenylcyclase which leads to an increase of cyclic AMP, responsible of its pharmacological effects.
- Hyperglycemia:
Glucagon has an hyperglycemic effect by increasing the transformation of glycogen into glucose and in parallel inhibiting the synthesis of glycogen from glucose.
It can be used in the emergency treatment in of hypoglycemic comas while waiting for the administration of glucose.
- Cardiovascular effect:
Glucagon has a positive inotropic effect and it increases cardiac output. It induces an arterial and venous vasodilator effect and decreases peripheral resistances. It can be used as an inotropic agent in the event of acute myocardial failure and in cases of beta-blocker overdosage..
- Effect on the digestive tract:
Glucagon reduces the motility of the digestive tract and can be used to facilitate radiological and endoscopical examinations of the digestive tract.
Glucagon is indicated primarily in the treatment of severe hypoglycaemia when the patient can not take glucose by mouth and when intravenous administration of glucose is not possible.. It is administered by intravenous, intramuscular or subcutaneous routes. Its effect is fast and of short duration, less than one half an hour, thus the need for supplementing its administration by that of glucose.
Glucagon has adverse effects: nausea, vomiting, reactional hypoglycemia after the phase of hyperglycemia, catecholamine release, rarely hypokalemia.
Antagonists of glucagon are under study.
Other hyperglycemic agents
- Catecholamines
By their beta effect catecholamines induc an hyperglycemic effect resulting from transformation of glycogen into glucose.
- Diazoxide
Diazoxide is an hyperglycemic sulphamide which, by increasing the efflux potassium out of the beta cell and cellular polarization, reduces insulin secretion and decreases vascular tone.
It is used by oral route to treat specific hypoglycemias like leucine-dependant hypoglycemia.
In injectable form, it is used in the treatment of the hypertensive emergency. Its hypotensive effect can be accompanied by an hypoglycaemia.
Diazoxide |
HYPERSTAT*,
PROGLYCEM* |
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