Which gland produces glucagon? The value of a blood test for glucagon concentration. Regulation of water-salt metabolism of hormones. Vasopressin and aldosterone: structure and mechanisms of action

Gross formula

C 153 H 225 N 43 O 49 S

Pharmacological group of the substance Glucagon

Nosological classification (ICD-10)

CAS code

16941-32-5

Characteristics of the substance Glucagon

Physiological insulin antagonist. Hormone produced by alpha cells of the islets of Langerhans; obtained from the pancreas of pigs or cattle and using genetic engineering methods. Crystalline white powder containing less than 0.05% zinc. Practically insoluble in water; dissolves well at pH below 3 and above 9.5.

Pharmacology

pharmachologic effect- antispasmodic, hyperglycemic.

It binds to specific receptors on the surface of cells of target organs (liver, skeletal muscles) and, indirectly, through Gs proteins, activates adenylate cyclase, an enzyme that converts ATP into cAMP, which, in turn, increases the activity of phosphorylase, which breaks down glycogen in the liver and muscles to glucose and inactivating glycogen synthetase, i.e. glycogenolysis and gluconeogenesis are stimulated. In other tissues (myocardium, smooth muscle) excites the second type of glucagon receptors, increases the concentration of intracellular inositol triphosphate, reduces the content of intracellular Ca 2+ and relaxes smooth muscles. At the same time, glucagon has a positive inotropic effect on the myocardium.

With intramuscular administration, Tmax is 13 minutes, Cmax is 6.9 ng/ml. With subcutaneous administration, Tmax is 20 minutes, Cmax is 7.9 ng/ml. Metabolized in the liver, kidneys, plasma, tissues during enzymatic proteolysis. T 1/2 - 3-6 min. Excreted by the kidneys.

The hyperglycemic effect manifests itself 5-20 minutes after intravenous administration, 15-26 minutes after intramuscular administration, 30-45 minutes after subcutaneous administration, the duration of the effect is up to 90 minutes. The antispasmodic effect after intravenous administration is observed after 45-60 s, after intramuscular administration - after 8-10 minutes (4-7 minutes after a dose of 2 mg); The duration of action depends on the dose and is 12-27 minutes (1 mg), 21-32 minutes (2 mg) after intravenous administration, 9-17 minutes (0.25-0.5 mg) after intravenous administration. , 22-25 min (2 mg).

Can be used for a number of diagnostic studies, incl.

for X-ray examination of the gastrointestinal tract using barium under conditions of artificial hypotension, angiography, computed tomography, MRI, diagnosis of bleeding from the small intestine using technetium-labeled erythrocytes, hysterosalpingography, as well as intoxication with beta-blockers and calcium channel blockers, obstruction of the esophagus by foreign bodies. There is evidence of use for shock therapy in patients with mental illness.

Use of the substance Glucagon

Hypoglycemia, hypoglycemic coma.

Contraindications

Hypersensitivity (including a history of pork and/or beef proteins), hyperglycemia, insulinoma (possible development of a paradoxical hypoglycemic reaction), pheochromocytoma (stimulating the release of catecholamines into the blood, can cause a sharp increase in blood pressure).

Use during pregnancy and breastfeeding

Does not cross the human placental barrier and can be used to treat severe hypoglycemia during pregnancy. It is unknown whether glucagon is excreted into breast milk. Since many drugs are excreted in milk in women, caution should be used when using glucagon during breastfeeding

. Clinical studies have not been conducted in nursing mothers, however, when prescribing the drug during breastfeeding, no risk to the child was noted.

Side effects of the substance Glucagon From the gastrointestinal tract:

nausea, vomiting. From the outside of cardio-vascular system and blood (hematopoiesis, hemostasis):

transient increase in blood pressure, tachycardia. Allergic reactions:

skin rashes and itching, urticaria, bronchospasm, anaphylactic shock. Other:

hypokalemia, dehydration.

Interaction

Enhances the effects of indirect anticoagulants.

Updating information

Interaction with beta-blockers

Against the background of beta-blockers, the administration of glucagon can lead to severe tachycardia and increased blood pressure. These effects are transient, because glucagon has a short half-life, however, in patients with pheochromocytoma or coronary artery disease, adjustment of therapy may be required.

A source of information

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[Updated

Interaction with propranolol
The hyperglycemic effect of glucagon can be reduced by propranol and possibly other beta blockers.
In a study of 5 healthy volunteers, the hyperglycemic effect of glucagon was reduced in the presence of propranolol. Under the influence of glucagon, blood glucose levels increased by 45%, but with subsequent administration of propranolol the increase was only 15%. The reason for this effect is unclear, but it can be assumed that propranolol inhibits the effects of catecholamines (glucagon stimulates the release of catecholamines). If this is true, then perhaps other beta blockers may have the same effect as propranolol. However, the clinical significance of this interaction is unclear.

Stockley's Drug Interactions/Ed. by Stockley.- 9th ed., 2010.- P. 1558.

rxlist.com 21.08.2013 ]

Interaction with indomethacin

When used together with indomethacin, glucagon may lose its ability to increase blood glucose and even cause hypoglycemia. When used in combination, caution must be exercised.

The pancreas performs exocrine and endocrine functions. Its exocrine part produces enzymes that are part of the digestive juice and ensure the digestion of food - the breakdown of large molecules into smaller ones. The endocrine apparatus of the gland consists of groups of cells known as the islets of Langerhans. They secrete a number of hormones into the blood:

glucagon;
somatostatin.

The main source of energy in human body– glucose. It is required for the functioning of all organs. Insulin and glucagon maintain its concentration in the blood at an optimal level, since a change in its quantity in one direction or another negatively affects the condition of the body. Insulin integrates special transporters into the membranes of cells of the liver, muscles, kidneys, etc., as a result of which glucose is absorbed by the cells. With a lack of insulin, sugar starvation of the organs develops and occurs. Glucagon is a counter-insular hormone. The coordinated work of hormones maintains carbohydrate balance.

The role of glucagon in the human body

Glucagon is a polypeptide hormone consisting of 29 amino acids. Glucagon is produced by alpha cells of the islet apparatus. The following functions of glucagon can be distinguished:

increases blood glucose levels (the main function of the hormone).

In the liver, glucose is stored in the form of glycogen. During fasting or prolonged physical activity, glucagon triggers a cascade of reactions by binding to liver receptors and leads to the breakdown of glycogen. Glucose is released and enters the blood, replenishing the body's energy needs.

Note! Glucagon does not lead to the breakdown of glycogen in muscles, since there are no specific receptors there.

activates new formation of glucose in the liver from non-carbohydrate components in case of its deficiency;
inhibits the use of glucose;
promotes the breakdown of fat reserves in the body. Therefore, when glucagon is produced, the content increases fatty acids in blood;
activates the formation of ketone bodies (special substances that, when broken down, provide the body with energy in conditions of deficiency of other sources, i.e. when there is no glucose);
stimulates insulin secretion in order to prevent excess glucose in the blood;
raises blood pressure by increasing the frequency and strength of heart contractions;
ensures the survival of the organism in extreme conditions by increasing potential energy sources in the blood (glucose, fatty acids, ketone bodies), which can be captured by organs and used for work;

High blood pressure also contributes better nutrition organs under stress.

stimulates the production of catecholamines by the adrenal medulla;
in superphysiological concentrations, relaxes the muscles of smooth muscle organs (antispasmodic effect);
The action of glucagon is helped by and, which also have a hyperglycemic effect.

Regulation of glucagon secretion

The human body is a well-coordinated system, so nature has developed mechanisms to maintain the level of glucagon in the blood at the proper level. The stimulus for alpha cell activation and glucagon secretion is:

decrease in glucose concentration. For long periods physical activity or fasting, its blood levels become critically low. The body experiences energy starvation and requires glucose. Glucagon is produced and releases glucose from reserves;
amino acids - arginine, alanine, which are released during the breakdown of protein supplied with food. The higher the protein content in food, the more glucagon is produced. Therefore, the diet should contain required amount complete proteins;
increasing insulin: to avoid excessive decrease in glucose;
hormones produced by the organs of the digestive system - gastrin, cholecystokinin;
medications - beta-agonists.

Inhibits glucagon secretion:

increased glucose, fatty acids or ketone bodies in the blood;
somatostatin, produced in the delta cells of the islet apparatus.

Proper functioning of the body requires an optimal balance between the processes of activation and inhibition of glucagon production, which maintains balance.

Composition and release form of the glucagon preparation

The hormone glucagon is not only produced in our body, but, if necessary, is administered externally in the form of drugs.

The glucagon drug is available in the form:

Lyophilized injection powder. The composition contains only glucagon. Packaged in glass bottles of 1, 2 or 5 ml, a solvent is attached to them;
Dry injection powder, which consists of glucagon and lactose hydrochloride/phenol solution with glycerin solution. Available in glass ampoules (666,667,668,669)

Glucagon for pharmaceutical powder is isolated from the pancreas of cattle or pigs. Surprisingly, the formula for human and animal glucagon has the same chemical structure. Another way to obtain it is through genetic engineering. The DNA that encodes the structure of glucagon is inserted into E. coli. The microorganism becomes a source of glucagon, which completely coincides in its amino acid composition with the human one.

Pharmacological action of the drug glucagon

The action of the synthetic glucagon drug is similar physiological effect endogenous hormone:

Breaks down glycogen in the liver into glucose, which then enters the blood. When the drug is administered into a vein, the effect is realized after 5-25 minutes, when administered intramuscularly - after 15-26 minutes, when administered subcutaneously - after 30-45 minutes, so it is necessary to wait time for the effect to manifest itself;
Relaxes smooth muscles (antispasmodic effect). When administered intravenously after 45 - 60 seconds, when administered intramuscularly after 8 - 10 minutes;
Increases the frequency of contraction of the heart muscle.

The instructions for use state that the effect does not develop in to the extent necessary after prolonged fasting, drinking alcohol. The amount of glycogen in the liver is reduced so much that glucagon cannot have a hyperglycemic effect.

With long-term use of glucagon, intestinal motility is inhibited and constipation develops.

Indications for use of the glucagon drug

hypoglycemia (a drop in blood glucose levels) and hypoglycemic coma (loss of consciousness caused by glucose deficiency);
overdose of calcium channel blockers and beta-blockers;
during diagnostic procedures: X-ray examination with barium of the digestive tract, angiographic examination of blood vessels, CT and magnetic resonance imaging to detect bleeding from the small intestine and other procedures where it is necessary to reduce muscle tone;
There are known facts about the use of glucagon for shock therapy in the treatment of mental illness.

Contraindications to the use of glucagon

hyperglycemia: when glucagon is produced, blood sugar rises even more;
hypersensitivity to beef and pork proteins in food;
(tumor of the islet apparatus of the pancreas), as this can lead to an unpredictable reaction - hypoglycemia);
(a tumor of the adrenal medulla that produces a large number of adrenaline. Since it is a glucagon synergist, it may lead to hyperglycemia;
(risk of hyperglycemia)

Note!
The hormone glucagon does not cross the placental barrier, so it can be used in pregnant women. However, it is not known for certain whether the drug passes into mother’s milk, so in this situation the drug should be used with caution;
Strengthens the effect of indirect anticoagulants.

Side effects

nausea and vomiting;
allergic reactions;
cardiopalmus;
promotion blood pressure.

Mode of application

Glucagon hormone is administered in various ways depending on the clinical situation - under the skin, into muscle tissue or into a vein. The dry component must be dissolved in the supplied solvent or in sterile water for injection. When you use glucagon, the instructions must be carefully studied to ensure the correct dosage is followed, that is:

To relieve hypoglycemia, 1 mg is administered intramuscularly. Depending on age, it is determined in what dosage to use the drug. Children under 5 years old 0.25 – 0.5 mg; children from 5 to 10 years old – 0.5 – 1 mg. Usually, glucagon is administered if it is not possible to administer glucose intravenously. If the measures were ineffective, then after 10 - 15 minutes the injection will have to be repeated;
When carrying out diagnostic procedures to examine the stomach or colon, glucagon is administered 0.5 mg intravenously or 2 mg intramuscularly;
When hit foreign body into the esophagus 0.5 - 2 mg intravenously.

Videos on the topic

An important organ of our body is the pancreas. It produces several hormones that affect the body's metabolism. These include glucagon, a substance that releases glucose from cells. In addition to it, the pancreas generates somatostatin and pancreatic polypeptide. Somatostatin is responsible for limiting the production of somatotropin and catecholamines (adrenaline, norepinephrine). The peptide regulates the functioning of the gastrointestinal tract. Insulin and glucagon control the content of the main source of energy - glucose, and these 2 hormones are directly opposite in action. What is glucagon and what other functions does it have, we will answer in this article.

Glucagon production and activity

Glucagon is a peptide substance that is produced by the islets of Langerhans and other cells of the pancreas. The parent of this hormone is preproglucagon.

Glucose obtained by the body from food has a direct effect on the synthesis of glucagon. Hormone synthesis is also affected protein products taken by a person during meals. They contain arginine and alanine, which increase the amount of the described substance in the body.

Glucagon synthesis is affected by physical work and sports. The greater the load, the greater the synthesis of the hormone. It also begins to be intensively produced during fasting. As a protective agent, the substance is produced during times of stress. Its surge is affected by the rise in level and .

Glucagon serves to form glucose from amino acids in proteins. Thus, it provides all organs with the energy necessary for functioning. human body. The functions of glucagon include:

the breakdown of glycogen in the liver and muscles, due to which the supply of glucose stored there is released into the blood and serves for energy metabolism;
the breakdown of lipids (fats), which also leads to the energy supply of the body;
formation of glucose from non-carbohydrate products;
ensuring increased blood supply to the kidneys;
increased blood pressure;
increased heart rate;
antispasmodic effect;
increased content of catecholamines;
stimulation of liver cell recovery;
accelerating the process of removing sodium and phosphorus from the body;
regulation of magnesium metabolism;
increase in calcium content in cells;
removal of insulin from cells.

It should be noted that in muscles, glucagon does not stimulate the production of glucose, since they do not have the necessary receptors that respond to the hormone. But from the list it is clear that the role of the substance in our body is quite large.

Glucagon and insulin are 2 opposing hormones. Insulin serves to store glucose in cells. It is produced when glucose levels are high, storing it in reserve. The mechanism of action of glucagon is that it releases glucose from cells and sends it to the organs of the body for energy metabolism. We must also take into account that some human organs absorb glucose, despite the functioning of insulin. These include the brain of the head, the intestines (some of its parts), the liver, and both kidneys. In order for the metabolism of sugar in the body to be balanced, other hormones are also needed - this is cortisol, the fear hormone adrenaline, which affects the growth of bones and tissues.

Hormone norm and deviations from it

The level of the hormone glucagon depends on the age of the person. In adults, the spread between the lower and upper values is smaller. The table looks like this:

Deviation from the norm in the volume of the hormone may indicate pathology. Including, when determining a reduced amount of a substance, the following are possible:

severe cystic fibrosis of the endocrine glands and respiratory organs;
chronic inflammation of the pancreas;
A decrease in glucagon levels occurs after operations to remove the pancreas.

The functions of glucagon are to eliminate some of the pathologies described above. An increased content of a substance indicates one of the situations:

increased glucose due to illness diabetes mellitus 1st type;
tumor lesion of the pancreas;
acute inflammation of the pancreas;
liver cirrhosis (degeneration of cells into tumor tissue);
excessive production of glucocorticoids due to their generation by tumor cells;
chronic kidney failure;
psychological stress.

If the hormone is exceeded or decreased, the doctor prescribes other tests for an accurate diagnosis. Blood biochemistry is done to determine glucagon levels.

Glucagon-containing agents

Glucagon synthesis is carried out from the hormone of animals, taking advantage of the fact that they have this substance of a similar structure. The medicine is available in the form of liquid for injection and in the form of tablets for oral administration. Injections are given intravenously or intramuscularly. The drug is prescribed in the following cases:

diabetes mellitus with low glucose levels;
additional treatment for depression;
the need to relieve spasm of the intestines;
to soothe and straighten smooth muscles;
for diseases of the biliary tract;
during radiological examination of the stomach.

The instructions describe that the dose of the injection, which is administered intravenously or, if it is impossible to inject a vein, intramuscularly, is 1 ml. After the injection, an increase in hormone levels, accompanied by an increase in the amount of glucose, is observed after 10 minutes.

The drug can be used to treat children. If the baby's weight is less than 20 kg, the dose should be no more than 0.5 ml. For heavier children, the dosage ranges from 0.5 to 1 ml. If the effect of the medication is insufficient, the injection is repeated after 12 minutes. You need to inject in a different place.

Treatment of children and pregnant women can only be carried out in a clinic under the supervision of a specialist. In preparation for radiation diagnostics, 0.25 mg to 2 mg of medication is injected. The dose, depending on the patient’s condition and weight, is calculated by the doctor. Taking the drug in any form without a doctor’s prescription is strictly prohibited.

If the medicine is being used as an emergency, after taking it, you should eat protein foods, drink a cup of warm, sweetened tea, and go to bed for 2 hours.

Contraindications to treatment with Glucagon

Glucagon should not be used for treatment in the following cases:

tumor disease of the pancreas with the production of insulin by tumor cells;
high sugar content;
with a benign or malignant tumor (pheochromocytoma), the cells of which generate catecholamines;
in case of individual intolerance to the drug.

Additional diagnostic procedures are required for early detection of contraindications to hormone treatment. Side effects from taking Glucagon may include nausea and vomiting. If the use of the medicine does not give the expected result, it is necessary to administer a glucose solution to the patient.

The drug can be used to treat pregnant women. It is retained by the placenta and does not reach the fetus. During the feeding period, the use of the drug is possible only under the strict supervision of a specialist.

If glucose is below normal, what to do?

Before the doctor arrives, you can increase your glucose level by eating certain foods. It's a good idea to eat 50 g of honey, which contains fructose, glucose and sucrose of natural origin. After all, only artificial fructose is harmful. And, if glucagon and glucose are not produced in sufficient quantity To supply us with glucose, we need to take sugar in the form of food.

Tea with jam will help restore strength. After severe overload or nervous stress It’s good to eat a lot of high-calorie foods. Their list includes seafood, nuts, apples, cheeses, pumpkin seeds, vegetable oils. Rest in a ventilated room and sound sleep will bring benefits.

Glucagon is a protein-peptide hormone that is produced in the islet apparatus of the pancreas. Special alpha cells of the organ are responsible for its synthesis, synthesizing exclusively these compounds. Glucagon (like cortisol and somatotropin) is a counter-insular hormone, that is, it has the opposite effect on carbohydrate metabolism than insulin. The production of glucagon is necessary to maintain adequate blood glucose levels, however, excess production of this hormone is one of the mechanisms for the development of type 2 diabetes.

Mechanism of action of glucagon

Glucagon's functions in the body are limited but very important. It increases blood glucose levels by activating glycogenolysis. Glycogen is a polysaccharide consisting of glucose monomer, found primarily in the liver and muscles.

When carbohydrates are consumed in the gastrointestinal tract, they are broken down. The glucose obtained during digestion under the influence of insulin is converted into glycogen, which is a “reserve depot” necessary to maintain an adequate level of glycemia in the event of a lack of carbohydrates in food or an increase in the need for them (during physical activity).

When the glycemic level decreases, counterinsular hormones are produced and released into the blood, which increase glucose levels in different ways. One of them is glucagon, the mechanism of action of which is to activate the enzymes necessary for glycogenolysis, resulting in the formation of glucose from glycogen, which is consumed by cells as an energy substrate.

Hormones responsible for carbohydrate metabolism are capable of regulating each other's secretion. An increase in glucagon levels leads to an increase in the concentration of insulin in the blood.

Diseases associated with disruption of hormone effects

At the moment, only one disease is known in the pathogenesis of which the role of glucagon has been reliably determined - type 2 diabetes mellitus. With this pathology, hormone synthesis increases, which leads to excessive activation of glycogenolysis and an increase in glycemia levels. It is worth noting that an increase in glucagon levels is only one of many links in the pathogenesis of diabetes and is far from the most significant.

The concentration of glucagon in the blood is not determined to diagnose diabetes mellitus. To date, laboratory criteria and reference intervals have not been developed to clearly distinguish normal indicators from diabetes mellitus. In addition, the level of the hormone increases with renal and liver failure, which makes this study unreliable.

There are hypoglycemic drugs, the mechanism of action of which is associated, among other things, with the suppression of glucagon secretion (type 1 glucagon-like peptide agonists, dipeptidyl peptidase-4 inhibitors).

Secondary diabetes mellitus can be the result of excessive secretion of the hormone - a tumor of the pancreas (glucogonoma). In this disease, glycogen levels are several times higher than the population average. In addition to carbohydrate metabolism disorders, pancytopenia, necrolytic migratory erythema, symptoms of metastatic damage to the liver and other internal organs (excruciating pain) are recorded. The tumor is usually detected quite late, at a stage that cannot be.

surgical treatment

Glycogen-based drug

There is a glucagon drug on the pharmaceutical market. The drug is intended to relieve hypoglycemia. These conditions occur predominantly in patients with diabetes mellitus who are on insulin therapy or taking sulfonylureas. The drug is available in finished form

in a container connected to a syringe, can be used for subcutaneous, intramuscular or intravenous injections. The possibility of subcutaneous and intramuscular administration makes this drug suitable for self-help (or for administration by the patient’s relatives).

Glucagon preparation

For a body weight of 20 kg or more, 1 mg of the drug is administered, for a lower weight - 500 mcg.

Glucagon is contraindicated for:
pheochromocytoma;
insulinoma;
glucagonoma;

individual intolerance. From side effects

possible:
vomiting, nausea;
skin rashes and itching;

arterial hypertension, sinus tachycardia. It is worth noting that the administration of the drug to relieve hypoglycemia is effective only in the presence of glycogen in the liver. Treatment of hypoglycemic conditions in fasting patients or patients eating only protein and significantly limiting carbohydrate intake using this medicine

not effective.

The main effects of Glucagon on glucose metabolism are as follows:

Glycogen is broken down in the liver, and the percentage of glucose in the blood increases within one to two minutes.
Gluconeogenesis increases.

The above effects lead to an increase in glucose levels in other human organs.

pharmachologic effect

Glucagon, whose functions are opposite to those of insulin, is not limited to only the hyperglycemic effect. It has an inotropic effect, i.e. the strength of heart contractions changes, chronotropic - a change in heart rate occurs, and Glucagon is aimed at relieving spasms. The listed effects on the heart arise as a result of the formation of cAMP in excess of normal levels.

CAMP is a messenger that serves to propagate the signals of certain hormones. If a person has high doses of Glucagon in the body, they can cause strong relaxation of the intestines.

An increase in the percentage of glucose concentration in human blood is caused by a complex of certain events:

1. The hormone Glucagon acts on adenylate cyclase, thereby activating it.

2. Then the process of cyclic adenosine monophosphate occurs.

3. After this, cAMP activates the protein kinase protein.

4. The processes listed above lead to the activation of protein kinase and phosphorylase B kinase.

5. Phosphorylase kinase “B” acts on phosphorylase “I”, thereby activating phosphorylase “A”. This process ensures the breakdown of glycogen, and then glucose-1-phosphate appears. Next, it is dephosphorylated, and after this, glucose is released from the liver cells.

This sequence of events is quite important, since cyclic adenosine monophosphate is able to function as a second messenger.

Indications for use

Hypoglycemia.
The drug is prescribed in cases of low blood sugar for patients with diabetes.
Used as shock therapy for various types of mental illness.
Used in diagnostics gastrointestinal tract as an aid.

Directions for use and dosage

Administration of Glucagon can be of three types: subcutaneous, intramuscular or intravenous. 1 milligram of Glucagon is indicated for children and adults whose weight is in the range of 20-25 kilograms. Children weighing less than 20 kg should receive a dose of 500 mcg.

To correctly calculate the dose, it is necessary to multiply the child’s body weight by 20 mcg of the drug. When necessary, the Glucagon injection can be repeated every 12 minutes. If it is used as a diagnostic, the dose can be either 500 mcg or 2 mg.

After the hormone Glucagon has been administered, experts recommend taking carbohydrates. They are designed to restore glycogen and also prevent secondary hypoglycemia. Sometimes it happens that the use of Glucagon does not produce visible results. Then it is necessary to administer intravenous glucose.

Hypoglycemia, hypoglycemic coma.

A tumor that produces excess Glucagon. It's called glucagonoma.
A tumor that overproduces insulin (insuloma).
A tumor that secretes catecholamines in excess.
As well as increased sensitivity to the drug.

In some cases, this product is prohibited for pregnant women and nursing mothers. Glucagon is prescribed to this category of people with caution.

Side effects of Glucagon

This drug may cause side effects such as vomiting, allergic reactions, increased blood pressure, and skin rashes.

The drug should be stored at a temperature of 15-30 degrees C.