Glucagon is a polypeptide that is secreted alpha cells islets of Langerhans and cells of the proximal digestive tract.

The main factor influencing hormone secretion is the concentration of glucose in the blood. A decrease in blood glucose concentration stimulates the secretion of glucagon, an increase depresses it.

RICE. 6.33. Regulatory circuit for glucagon secretion. C - concentration

They activate the secretion of glucagon, in addition to glucose, amino acids (arginine, alanine), a decrease in the level of fatty acids in the blood and hormones of the digestive tract: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP) and physical activity.

Regulation of glucagon secretion

The regulated parameter in the glucagon secretion regulatory circuit is the glucose concentration. Reducing it in the blood stimulates alpha cells, which increase the secretion of the hormone, which leads to an increase in the concentration of glucose, which, through negative feedback, reduces the secretion of glucagon (Fig. 6.33).

An increase in glucagon secretion causes an increase in the concentration of amino acids in the blood (especially arginine), cholecystokinin, catecholamines, and acetylcholine.

A decrease in glucagon secretion occurs with an increase in: the concentration of blood glucose, insulin, somatostatin, fatty acids and ketones.

The mechanism of action of glucagon on target cells

Glucagon mainly affects liver target cells, in the membranes of which serpentine receptors are located. Hormone-receptor complex via stimulating G5 protein activates adenylate cyclase, which leads to the formation of an intracellular messenger cAMP, which activates protein kinase A. The latter potentiates phosphorylase, which leads to an increase in the breakdown of glycogen in the liver and an increase in the concentration of glucose in the blood.

Glucagon also acts through other receptors in hepatocytes, binding to which leads to activation phospholipases C, the consequence of which is an increase in the concentration of Ca 2+ ions in the cytoplasm, stimulating glycogenolysis.

Physiological effects of glucagon

Regulation of carbohydrate metabolism Glucagon increases blood glucose concentration by stimulating glycogenolysis in the liver and prevents the formation of glycogen. However, the hyperglycemic effect of glucagon does not lead to a decrease in glucose utilization by peripheral cells.

Glucagon increases gluconeogenesis in the liver. It reduces the formation of fructose-2,6-diphosphate and inhibits the activity of phosphofructokinase, which leads to the release of glucose from the liver.

Regulation of fat metabolism Glucagon increases concentration fatty acids And ketones in the blood thanks to the following mechanisms :

1 increases lipolysis, suppresses the synthesis of fatty acids, directing substrates in the direction of gluconeogenesis;

2 forms ketones(β-hydroxybutyrate and acetoacetate) with malonyl coenzyme. And with the degradation of fatty acids, in the absence of insulin, glucagon can accelerate ketogenesis, which will lead to metabolic acidosis.

Regulation of protein metabolism Glucagon stimulates gluconeogenesis enzymes (pyruvate carboxylase and fructose-1,6-biphosphatases), which convert proteins into glucose. In addition to the catabolic effect, the hormone has an anti-anabolic effect - it suppresses protein synthesis.

The human body is a well-oiled mechanism that works every second. Hormones play an important role in ensuring its continuous operation.

The central nervous system sends electrical impulses to all systems and organs. In turn, the endocrine system secretes insulin, glucagon and other necessary hormones for the continuous functioning of the human body.

The exocrine and endocrine systems are components of the primary gut. In order for food entering the body to be broken down into proteins, fats and carbohydrates, it is important that the exocrine system functions fully.

It is this system that produces at least 98% of digestive juice, which contains enzymes that break down foods. In addition, hormones regulate all metabolic processes in the body.

The main hormones of the pancreas are:

1. Insulin,
2. C-peptide,
3. Insulin,
4. Glucagon.

All pancreatic hormones, including glucagon and insulin, are closely related to each other. Insulin has the role of ensuring glucose stability; in addition, it maintains the level of amino acids for the body to function.

Glucagon acts as a kind of stimulant. This hormone binds together all the necessary substances, sending them into the blood.

The hormone insulin can only be produced when blood glucose levels are high. The function of insulin is to bind receptors on cell membranes, it also delivers them into the cell. Then glucose is transformed into glycogen.

However, not all organs need insulin as a storehouse of glucose. Glucose is absorbed regardless of insulin in cells:

• Intestines,
• Brain,
• Liver,
• Kidneys.

If, on the contrary, the hormone insulin is produced in large quantities in the pancreas, then glucose is very quickly utilized and its concentration in the blood drops sharply, leading to hypoglycemia. This condition also leads to quite serious consequences, including hypoglycemic coma.

The role of glucagon in the body

The hormone glucagon is involved in the formation of glucose in the liver and regulates its optimal content in the blood. For the normal functioning of the central nervous system, it is important to maintain the concentration of glucose in the blood at a constant level. This is approximately 4 grams per 1 hour for the central nervous system.

The effect of glucagon on glucose production in the liver is determined by its functions. Glucagon has other functions, it stimulates the breakdown of lipids in adipose tissue, which seriously reduces blood cholesterol levels. In addition, the hormone glucagon:

1. Increases blood flow in the kidneys;
2. Increases the rate of sodium excretion from organs and also maintains optimal electrolyte ratio in the body. A is an important factor in the functioning of the cardiovascular system;
3. Regenerates liver cells;
4. Stimulates the release of insulin from body cells;
5. Increases intracellular calcium content.

An excess of glucagon in the blood leads to the appearance of malignant tumors in the pancreas. However, it is rare, it appears in 30 people out of a thousand.

The functions performed by insulin and glucagon are diametrically opposed. Therefore, other important hormones are required to maintain blood glucose levels:

1. cortisol,
2. adrenalin,
3. somatotropin.

Regulation of glucagon secretion

Increasing the consumption of protein foods leads to an increase in the concentration of amino acids: arginine and alanine.

These amino acids stimulate the production of glucagon in the blood, so it is extremely important to ensure a stable supply of amino acids in the body by adhering to a nutritious diet.

The hormone glucagon is a catalyst that converts amino acids into glucose; these are its main functions. Thus, the concentration of glucose in the blood increases, which means that the cells and tissues of the body are supplied with all the necessary hormones.

In addition to amino acids, glucagon secretion is also stimulated by active physical exercise. Interestingly, they must be carried out to the limit of human capabilities. It is then that the concentration of glucagon increases fivefold.

Pharmacological action of the drug glucagon

Glucagon works as follows:

• reduces spasms,
• changes the number of heartbeats,
• increases the amount of glucose in the body due to the breakdown of glycogen and its formation as a combination of other organic elements.

Indications for use of the medicinal product

The drug glucagon is prescribed by doctors in the following cases:

1. Mental disorders, as shock therapy,
2. Diabetes mellitus with a concomitant diagnosis of hypoglycemia (low blood glucose levels),
3. Instrumental and laboratory studies of the gastrointestinal tract, as an auxiliary drug,
4. The need to eliminate spasm in acute diverculitis,
5. Biliary tract pathologies,
6. To relax the smooth muscles of the intestines and abdomen.

Instructions for use of glucagon

To use the hormone for medicinal purposes, it is obtained from the pancreas of animals such as a bull or pig. It is interesting that the sequence of amino acids in the chain in these animals and humans is absolutely identical.

For hypoglycemia, 1 milligram of glucagon is prescribed intravenously or intramuscularly. If it is necessary to provide emergency assistance, these are the methods of drug administration that are used.

Following the exact instructions for using the hormone glucagon shows that improvement in a patient with low blood sugar occurs within 10 minutes. This will reduce the risks of damage to the central nervous system.

Please note that it is prohibited to administer glucagon to children weighing up to 25 kilograms. Babies need to administer a dose of up to 500 mg and observe the state of the body for 15 minutes.

If everything is normal, you need to increase the dose by 30 mcg. In case of depletion of glucagon reserves in the liver, it is necessary to increase the dose of the drug several times. It is forbidden to make your own decision about using the drug.

As soon as the patient’s condition improves, it is recommended to eat protein foods, drink warm sweet tea and take a horizontal position for 2 hours to avoid relapse.

If the use of glucagon does not produce results, it is recommended to administer glucose intravenously. Side effects after using glucagon are gagging and nausea.

After depletion of the glycogen depot in the liver against the background of further administration of glucagon, parallel developing hyperglycemia can be observed. This is the result of an increase in the supply of amino acids into liver cells under the influence of glucagon, followed by their conversion into glucose as a result of gluconeogenesis. This effect is achieved by the activation of multiple enzymes necessary for amino acid transport and gluconeogenesis, especially enzyme systems that convert pyruvate to phosphoenolpyruvate, which is the rate-limiting step in gluconeogenesis.

Most other effects are detected when its concentration in the blood exceeds the maximum value. Perhaps one of the most important effects of glucagon is the activation of lipase in fat cells, providing an increase in the amount of free fatty acids that can be used in the body's energy supply processes. Glucagon also prevents the storage of triglycerides in the liver, which prevents the removal of fatty acids from the blood by hepatocytes. This makes them more accessible to other body tissues.

Glucagon in very high concentrations also: (1) increases heat generation; (2) increases blood flow in some tissues, especially the kidneys; (3) increases bile secretion; (4) inhibits the secretion of hydrochloric acid in the stomach. It is possible that all these influences are not significant under conditions of normal functioning of the body.

Regulation of glucagon secretion

Concentration glucose in the blood is the most significant factor controlling glucagon production.
However, we specifically emphasize the nature of the influence of blood glucose concentration on glucagon production, which is directly opposite to the influence of this factor on insulin secretion.

The figure shows that the decrease in concentration glucose in the blood from the level accompanying the fasting state, i.e. 90 mg/dL of blood, to a level characterizing hypoglycemia, can increase the concentration of glucagon in plasma several times. On the contrary, an increase in blood glucose concentration to hyperglycemic values ​​is accompanied by a decrease in plasma glucagon concentration. Thus, during hypoglycemia, glucagon is secreted in greater quantities, which subsequently causes an increase in glucose output from the liver and is therefore an important means of compensating for hypoglycemia.

An increase in amino acids in the blood stimulates production. The high concentration of amino acids in the blood that occurs after eating protein foods (especially the amino acids alanine and arginine) stimulates the secretion of glucagon. This effect is similar to that which amino acids had on insulin production. Thus, the changes in the secretion of glucagon and insulin that occur in this case are not of a multidirectional nature. The importance of amino acid stimulation of glucagon production is that glucagon ensures the rapid conversion of amino acids into glucose, increasing the amount of glucose available to tissues.

Physical exercise stimulate glucagon secretion. Against the background of exhausting physical activity, the concentration of glucagon in the blood increases 4-5 times. It is not clear what causes this, because... the concentration of glucose in the blood may not decrease. The beneficial effect of glucagon in this situation is that it prevents the decrease in blood glucose levels.

One of factors What may increase glucagon production under these conditions is an increase in circulating amino acids. Along with this, adrenergic stimulation of the islets of Langerhans may also contribute.

The “hunger hormone” glucagon is little known in comparison with insulin, although these two substances work closely together and play an equally important role in our body. Glucagon is one of the main hormones of the pancreas, which, together with insulin, is responsible for regulating blood glucose levels. Hormonal preparations based on it are actively used in medicine for recovery from diabetes mellitus and preparation for gastrointestinal tract diagnostics.

Structure and synthesis of glucagon

Glucagon is called differently, but most often it is referred to as an insulin antagonist hormone. Scientists H. Kimball and J. Murlin discovered a new substance in the pancreas in 1923, 2 years after the historical discovery of insulin. But few people knew about the irreplaceable role of glucagon in the body.

Today, medicine uses 2 main functions of the “hunger hormone” - hyperglycemic and diagnostic, although in fact the substance performs several important tasks in the body at once.

Glucagon is a protein, or more precisely, a peptide hormone in its chemical structure. In structure, it is a single-chain polypeptide consisting of 29 amino acids. It is formed from preproglucagon, an even more powerful polypeptide consisting of 180 amino acids.

Despite the importance of glucagon in the body, its amino acid structure is quite simple, and in scientific terms, “highly conservative.” So, in humans, cows, pigs and rats the structure of this hormone is absolutely the same. Therefore, glucagon preparations are usually obtained from the pancreas of a bovine or pig.

Functions and effects of glucagon in the body

Glucagon secretion occurs in the endocrine part of the pancreas under the intriguing name “islets of Langerhans”. A fifth of these islets are made up of special alpha cells, which produce the hormone.

Glucagon production is influenced by 3 factors:

1. The concentration of glucose in the blood (a drop in sugar levels to a critical level can provoke an increase in the volume of the “hunger hormone” in the plasma several times).
2. Increasing the amount of amino acids in the blood, especially alanine and arginine.
3. Active physical activity (exhausting training at the limit of human capabilities increases the concentration of the hormone by 4-5 times).

Once in the blood, the “hunger hormone” rushes to the receptors of liver cells, binds to them and stimulates the release of glucose into the blood, maintaining it at a stable, constant level. Also, the pancreatic hormone glucagon performs the following tasks in the body:

• activates the breakdown of lipids and lowers cholesterol levels in the blood
• increases blood flow in the kidneys
• promotes rapid removal of sodium from the body (and this improves heart function)
• participates in the regeneration of liver cells
• stimulates the release of insulin from cells

Glucagon is also an indispensable ally of adrenaline in ensuring the body’s “fight or flight” response. When adrenaline is released into the blood, glucagon increases the volume of glucose almost instantly to fuel skeletal muscles and increases the supply of oxygen to the muscles.

The norm of glucagon in the blood and its disorders

The level of glucagon in the blood differs for children and adults. In children 4-14 years old, the level of “hunger hormone” can vary between 0-148 pg/ml; for adults, a range of 20-100 pg/ml is allowed. But if the glucagon level drops or rises below standard values, this can signal a variety of problems in the body.

A decrease in glucagon levels in the blood often indicates cystic fibrosis, chronic pancreatitis, and is diagnosed after pancreatectomy (removal of the pancreas).

An increase in hormone levels is a possible sign of the following pathologies:

• type 1 diabetes mellitus
• glucagonoma (tumor of the alpha cell zone in the pancreas)
• acute pancreatitis
• cirrhosis of the liver
• Cushing's syndrome
• chronic renal failure
• acute hypoglycemia
• any severe stress (injuries, burns, surgeries, etc.)

Indications for use of the glucagon drug

Synthetic glucagon is used in medicine in two cases. First purpose– this is the correction of severe forms of hypoglycemia, when for some reason glucose infusion (dropper) is impossible. Second meaning glucagon – preparation of examination of the upper and lower gastrointestinal tract, especially for radiological diagnostics.

Glucagon-like peptide can also be used to treat type 2 diabetes. This substance has a structure similar to glucagon, but is an incretin - synthesized in the intestines after eating. The drug is designed to correct glucose levels, in some cases even without additional insulin.

The list of indications for taking hormonal glucagon preparations includes:

• shock therapy for patients with mental disorders
• diabetes mellitus with simultaneous hypoglycemia
• auxiliary drug for laboratory diagnostics
• relieving spasms in acute intestinal diverticulosis
• relaxation of smooth muscles of the stomach and intestines

Method of use of glucagon and contraindications

There are 3 main options for glucagon injection - intravenous, intramuscular and subcutaneous. If emergency assistance is required (for example, in case of hypoglycemic coma), exclusively the first two options are used.

The standard dose of a hormonal drug for medicinal purposes is 1 mg. Improvement usually occurs within 10 minutes. To prepare for diagnosis, 0.25-2 mg is needed, the dosage is determined by the attending physician.

There are special recommendations for the use of the drug for children and pregnant women. Since glucagon does not cross the placental barrier, You can use it while pregnant. But - only in emergency cases and according to the doctor's decision. The use of glucagon drugs for children weighing less than 20-25 kg is not recommended. If absolutely necessary, a dose of 500 mcg is administered and the young patient's condition is carefully monitored for 15 minutes. If necessary, you can increase the dose by 20-30 mcg.

When treating with glucagon drugs, the recovery period is also very important. After improvement, the patient needs protein foods, sweet tea and complete rest for 2-3 hours. If hormonal medication does not help, intravenous glucose is required.

For the full functioning of the human body, the coordinated work of all its organs is necessary. A lot of this depends on the production of hormones and their sufficient content.

One of the organs responsible for the synthesis of hormones is the pancreas. It produces several types of hormones, including glucagon. What are its functions in the human body?

Pancreatic hormones

When there are disturbances in the functioning of the human body, various factors must be taken into account. They can be external and internal. Among the internal factors that can trigger the development of pathological changes are an excess or deficiency of a certain type of hormone.

To eliminate the problem, you need to know which gland produces this or that type of compound in order to take the necessary measures.

The pancreas produces several types of hormones. The main one is insulin. It is a polypeptide containing 51 amino acids. With insufficient or excessive formation of this hormone in the human body, deviations occur. Its normal values ​​range from 3 to 25 µU/ml. In children, its level is slightly reduced; in pregnant women it may increase.

Insulin is necessary to reduce the amount of sugar. It activates the absorption of glucose by muscle and fat tissue, ensuring its conversion into glycogen.

In addition to insulin, the pancreas is responsible for the synthesis of hormones such as:

1. C-peptide. It is not a complete hormone. In fact, it is one of the elements of proinsulin. It is separated from the main molecule and ends up in the blood. C-peptide is the equivalent of insulin, the amount of which can be used to diagnose pathologies in the liver and pancreas. It also indicates the development of diabetes mellitus.
2. Glucagon. In its action, this hormone is the opposite of insulin. Its peculiarity is an increase in sugar levels. This is achieved due to its effect on the liver, which stimulates the production of glucose. Glucagon also helps break down fats.
3. Pancreatic polypeptide. This hormone was recently discovered. Thanks to it, the consumption of bile and digestive enzymes is reduced, which is ensured by the regulation of the activity of the gallbladder muscles.
4. Somatostatin. It affects the functioning of other pancreatic hormones and enzymes. Under its influence, the amount of glucagon, hydrochloric acid and gastrin decreases, and the process of carbohydrate absorption slows down.

In addition to these hormones, the pancreas produces others. The activity of the body and the risk of developing pathologies depend on how much their quantity corresponds to the norm.

Functions of glucagon in the body

To better understand the role of glucagon in the human body, it is necessary to consider its functions.

This hormone affects the functioning of the central nervous system, which depends on the constant concentration of glucose in the blood. Glucose is produced by the liver, and glucagon is involved in this process. It also regulates its amount in the blood. Thanks to its action, lipids break down, which helps reduce the amount of cholesterol. But these are not the only functions of this hormone.

In addition to them, it performs the following actions:

• stimulates blood flow in the kidneys;
• promotes the excretion of sodium, normalizing the activity of the cardiovascular system;
• restores liver cells;
• increases calcium content inside cells;
• supplies the body with energy by breaking down lipids;
• normalizes cardiac activity, affecting pulse rate;
• increases blood pressure.

Its effect on the body is considered opposite to that of insulin.

Chemical nature of the hormone

The biochemistry of this compound is also very important to fully understand its significance. It arises from the activity of the alpha cells of the islets of Langenhans. It is also synthesized by other parts of the gastrointestinal tract.

Glucagon is a single chain polypeptide. It contains 29 amino acids. Its structure is similar to insulin, but it contains some amino acids that are absent in insulin (tryptophan, methionine). But cystine, isoleucine and proline, which are present in insulin, are not present in glucagon.

This hormone is formed from pre-glucagon. The process of its production depends on the amount of glucose that enters the body during meals. Stimulation of its production belongs to arginine and alanine - with an increase in their amount in the body, glucagon is formed more intensely.

With excessive physical activity, its amount can also increase sharply. Insulin also affects its level in the blood.

Mechanism of action

The main site of action of this compound is the liver. Under its influence, glycogenolysis occurs in this organ first, and a little later - ketogenesis and gluconeogenesis.

This hormone cannot enter the liver cells on its own. To do this, it has to interact with receptors. When glucagon interacts with the receptor, adenylate cyclase is activated, which promotes the production of cAMP.

As a result, the process of glycogen breakdown begins. This indicates the body’s need for glucose, so it actively enters the blood during glycogenolysis. Another option is to synthesize it from other substances. This is called gluconeogenesis.

It is also an inhibitor of protein synthesis. Its effect is often accompanied by a weakening of the process of glucose oxidation. The result is ketogenesis.

This compound does not affect glycogen contained in skeletal muscles, which is explained by the absence of receptors in them.

Its physiological antagonist is insulin. Therefore, its effect is most intense when there is a lack of insulin. This hormone begins to be actively produced when there is an increased content of glucagon in the body in order to prevent the development of hyperglycemia.

The increase in cAMP caused by glucagon leads to inotropic and chronotropic effects on the myocardium. As a result, a person’s blood pressure increases, heart contractions become stronger and more frequent. This ensures activation of blood circulation and replenishment of tissues with nutrients.

A large amount of this compound causes an antispasmodic effect. In humans, the smooth muscles of the internal organs relax. This is most pronounced in relation to the intestines.

Glucose, keto acids and fatty acids are energy substrates. Under the influence of glucagon, they are released, making them available to the skeletal muscles. Thanks to active blood flow, these substances are better distributed throughout the body.

What does excess and lack of hormones in the body lead to?

The most basic effect of the hormone is an increase in the amount of glucose and fatty acids. Whether this is good or bad depends on how much glucagon is synthesized.

If there are deviations, it begins to be produced in large quantities - such that it is dangerous for the development of complications. But too little of it, caused by malfunctions in the body, leads to adverse consequences.

Excessive production of this compound leads to an oversaturation of the body with fatty acids and sugar. Otherwise, this phenomenon is called hyperglycemia. A single case of its occurrence is not dangerous, but systematic hyperglycemia leads to the development of disorders. It may be accompanied by tachycardia and a constant increase in blood pressure, which leads to hypertension and cardiac pathologies.

Too active movement of blood through the vessels can cause their premature wear, which causes vascular diseases.

But the most dangerous is the likelihood of developing cancer cells. Excess glucagon can provoke this phenomenon. The pancreas is especially vulnerable in this case.

With an abnormally small amount of this hormone, the human body experiences a lack of glucose, which leads to hypoglycemia. This condition is also dangerous and pathological, as it can cause a lot of unpleasant symptoms.

These include:

• nausea;
• dizziness;
• tremor;
• low performance;
• weakness;
• clouding of consciousness;
• convulsions.

In especially severe cases, the patient's death may occur.

Video material about the effect of glucagon on a person’s weight:

Based on this, we can say that, despite many useful features, the content of glucagon in the body should not go beyond normal limits.