Hormonal preparations of the pancreas. The biological role of pancreatic hormones

Antithyroid drugs are used for hyperfunction of the thyroid gland (thyrotoxicosis, Graves' disease). Currently, the most commonly used antithyroid drugs are thiamazole (mercasolil), which inhibits thyroperoxidase and thus prevents iodination of tyrosine residues of thyroglobulin and disrupts the synthesis of T 3 and T 4 . Assign inside. When using this drug, leukopenia, agranulocytosis, skin rashes are possible. Possible enlargement of the thyroid gland.

As antithyroid drugs, iodides are prescribed orally - kalia iodide or sodium iodide in sufficiently high doses (160-180 mg). In this case, iodides reduce the production of thyroid-stimulating hormone by the pituitary gland; accordingly, the synthesis and release of T 3 and T 4 are reduced. A similar inhibition of the release of thyroid-stimulating hormone is also observed when using diiodotyrosine. The drugs are taken orally. Causes a decrease in the volume of the thyroid gland. Side effects: headache, lacrimation, conjunctivitis, pain in the salivary glands, laryngitis, skin rashes.

3. Preparation of the hormone of parafollicular cells of the thyroid gland

Parafollicular cells of the thyroid gland secrete calcitonin, which prevents bone decalcification by reducing osteoclast activity. The consequence of this is a decrease in the content of calcium ions in the blood. A drug calcitonin used for osteoporosis.

Parathyroid hormone drug

The polypeptide hormone of the parathyroid glands parathyroid hormone affects the exchange of calcium and phosphorus. Causes decalcification of bone tissue. Promotes the absorption of calcium ions from the gastrointestinal tract, increases calcium reabsorption and reduces phosphate reabsorption in the renal tubules. In this regard, when acting parathyroid hormone increases the level of Ca 2+ in the blood plasma. Medicinal product from the parathyroid glands of slaughtered cattle parathyroidin used for hypoparathyroidism, spasmophilia.

Pancreatic hormone preparations

The pancreas is an endocrine and exocrine gland. β-cells of the islets of Langerhans produce insulin, α-cells produce glucagon. These hormones have an opposite effect on blood glucose levels: insulin lowers it, and glucagon raises it.

1. Insulin preparations and synthetic hypoglycemic agents

Insulin stimulates tyrosine kinase-coupled receptors on cell membranes. As a result, insulin

promotes the uptake of glucose by tissue cells (with the exception of the central nervous system), facilitating the transport of glucose through cell membranes;

reduces gluconeogenesis in the liver;

3) stimulates the formation of glycogen and its deposition in the liver;

4) promotes the synthesis of proteins and fats and prevents their catabolism;

5) reduces glycogenolysis in the liver and skeletal muscles.

With insufficient production of insulin, diabetes mellitus develops, in which carbohydrate, fat and protein metabolism is disturbed.

Type I diabetes mellitus (insulin-dependent) is associated with the destruction of β-cells of the islets of Langerhans. The main symptoms of type I diabetes mellitus are: hyperglycemia, glucosuria, polyuria, thirst, polydipsia (increased fluid intake), ketonemia, ketonuria, ketacidosis. Severe forms of diabetes without treatment are fatal; death occurs in a state of hyperglycemic coma (significant hyperglycemia, acidosis, unconsciousness, the smell of acetone from the mouth, the appearance of acetone in the urine, etc.). In type I diabetes, the only effective means are insulin preparations, which are administered parenterally.

Type II diabetes mellitus (non-insulin-dependent) is associated with a decrease in insulin secretion (decrease in β-cell activity) or with the development of tissue resistance to insulin. Insulin resistance may be associated with a decrease in the number or sensitivity of insulin receptors. In this case, insulin levels may be normal or even elevated. Elevated insulin levels contribute to obesity (an anabolic hormone), which is why type 2 diabetes is sometimes called obese diabetes. In type II diabetes mellitus, oral hypoglycemic agents are used, which, if they are insufficiently effective, are combined with insulin preparations.

Insulin preparations

Currently, the best insulin preparations are recombinant human insulin preparations. In addition to them, preparations of insulin obtained from the pancreas of pigs (pork insulin) are used.

Human insulin preparations are produced by genetic engineering.

human insulin soluble(Actrapid NM) is produced in 5 and 10 ml bottles containing 40 or 80 IU per 1 ml, as well as in 1.5 and 3 ml cartridges for syringe pens. The drug is usually injected under the skin 15-20 minutes before meals 1-3 times a day. The dose is selected individually depending on the severity of hyperglycemia or glucosuria. The effect develops after 30 minutes and lasts 6-8 hours. Lipodystrophy can develop at the sites of subcutaneous insulin injections, so it is recommended to constantly change the injection site. In a diabetic coma, insulin can be given intravenously. In the event of an overdose of insulin, hypoglycemia develops. There are pallor, sweating, a strong feeling of hunger, trembling, palpitations, irritability, tremor. Hypoglycemic shock may develop (loss of consciousness, convulsions, disruption of the heart). At the first sign of hypoglycemia, the patient should eat sugar, biscuits, or other glucose-rich foods. In case of hypoglycemic shock, glucagon or intravenous 40% glucose solution is administered intramuscularly.

Zinc-suspension crystalline human insulin(ultratard HM) is administered only under the skin. Insulin is slowly absorbed from the subcutaneous tissue; the effect develops after 4 hours; maximum effect after 8-12 hours; the duration of action is 24 hours. The drug can be used as a basic agent in combination with fast and short-acting drugs.

Porcine insulin preparations are similar in action to human insulin preparations. However, when using them, allergic reactions are possible.

Insulinsolubleneutral is available in 10 ml vials containing 40 or 80 IU per 1 ml. Enter under the skin 15 minutes before meals 1-3 times a day. Perhaps intramuscular and intravenous administration.

Insulin- zincsuspensionamorphous it is injected only under the skin, providing slow absorption of insulin from the injection site and, accordingly, a longer action. Beginning of action after 1.5 hours; peak action after 5-10 hours; duration of action - 12-16 hours.

Insulin-zinc suspension crystalline injected only under the skin. Beginning of action in 3-4 hours; peak action after 10-30 hours; duration of action 28-36 hours.

Synthetic hypoglycemic agents

The following groups of synthetic hypoglycemic agents are distinguished:

1) sulfonylurea derivatives;

2) biguanides;

Derivatives of sulfonylurea - butamide, chlorpropamide, glibenclamide administered internally. These drugs stimulate the secretion of insulin by the β-cells of the islets of Langerhans.

The mechanism of action of sulfonylurea derivatives is associated with blockade of ATP-dependent K + channels of β-cells and depolarization of the cell membrane. At the same time, voltage-dependent Ca 2+ channels are activated; Ca r+ input stimulates insulin secretion. In addition, these substances increase the sensitivity of insulin receptors to the action of insulin. It has also been shown that sulfonylurea derivatives increase the stimulating effect of insulin on the transport of glucose into cells (fat, muscle). Sulfonylureas are used in type II diabetes mellitus. Not effective for type I diabetes. Absorbed in the gastrointestinal tract quickly and completely. Most of it binds to plasma proteins. Metabolized in the liver. Metabolites are excreted mainly by the kidneys, and can be partially excreted in the bile.

Side effects: nausea, metallic taste in the mouth, pain in the stomach, leukopenia, allergic reactions. With an overdose of sulfonylurea derivatives, hypoglycemia is possible. The drugs are contraindicated in violations of the liver, kidneys, blood system.

Biguanides - metformin administered internally. Metformin:

1) increases the uptake of glucose by peripheral tissues, especially muscles,

2) reduces gluconeogenesis in the liver,

3) reduces the absorption of glucose in the intestine.

In addition, metformin reduces appetite, stimulates lipolysis and inhibits lipogenesis, resulting in a decrease in body weight. Prescribed for type II diabetes. The drug is well absorbed, the duration of action is up to 14 hours. Side effects: lactic acidosis (increased levels of lactic acid in the blood plasma), pain in the heart and muscles, shortness of breath, and a metallic taste in the mouth, nausea, vomiting, diarrhea.

Pancreatic hormone preparations

The human pancreas, mainly in its caudal part, contains approximately 2 million islets of Langerhans, which make up 1% of its mass. The islets consist of a-, b- and l-cells that produce respectively glucagon, insulin and somatostatin (inhibiting the secretion of growth hormone).

In this lecture, we are interested in the secret of b-cells of the islets of Langerhans - INSULIN, since insulin preparations are currently the leading antidiabetic agents.

Insulin was first isolated in 1921 by Banting, Best - for which they received the Nobel Prize in 1923. Isolated insulin in crystalline form in 1930 (Abel).

Normally, insulin is the main regulator of blood glucose levels. Even a slight increase in blood glucose causes the secretion of insulin and stimulates its further synthesis by b-cells.

The mechanism of action of insulin is due to the fact that homon enhances the uptake of glucose by tissues and promotes its conversion into glycogen. Insulin, by increasing the permeability of cell membranes for glucose and lowering the tissue threshold to it, facilitates the penetration of glucose into cells. In addition to stimulating the transport of glucose into the cell, insulin stimulates the transport of amino acids and potassium into the cell.

Cells are very permeable to glucose; in them, insulin increases the concentration of glucokinase and glycogen synthetase, which leads to the accumulation and deposition of glucose in the liver in the form of glycogen. In addition to hepatocytes, glycogen depots are also striated muscle cells.

With a lack of insulin, glucose will not be properly absorbed by the tissues, which will be expressed by hyperglycemia, and with very high blood glucose numbers (more than 180 mg / l) and glucosuria (sugar in the urine). Hence the Latin name for diabetes: "Diabetes mellitus" (sugar diabetes).

Tissue requirements for glucose vary. in a number of fabrics

The brain, cells of the visual epithelium, the seminal epithelium - the formation of energy occurs only due to glucose. Other tissues may use fatty acids in addition to glucose for energy production.

In diabetes mellitus (DM), a situation arises in which, in the midst of "abundance" (hyperglycemia), cells experience "hunger".

In the patient's body, in addition to carbohydrate metabolism, other types of metabolism are also perverted. With insulin deficiency, a negative nitrogen balance is observed, when amino acids are predominantly used in gluconeogenesis, this wasteful conversion of amino acids into glucose, when 56 g of glucose is formed from 100 g of protein.

Fat metabolism is also disturbed, and this is primarily due to an increase in the level of free fatty acids (FFA) in the blood, from which ketone bodies (acetoacetic acid) are formed. The accumulation of the latter leads to ketoacidosis up to coma (coma is the extreme degree of metabolic disturbance in diabetes). In addition, under these conditions, cell resistance to insulin develops.

According to the WHO, at present, the number of patients with diabetes on the planet has reached 1 billion people. In terms of mortality, diabetes ranks third after cardiovascular pathology and malignant neoplasms, so diabetes is the most acute medical and social problem that requires emergency measures to be addressed.

According to the current WHO classification, the population of patients with diabetes is divided into two main types.

1. Insulin-dependent diabetes mellitus (formerly called juvenile) - IDDM (DM-I) develops as a result of progressive death of b-cells, and therefore is associated with insufficient insulin secretion. This type debuts before the age of 30 and is associated with a multifactorial type of inheritance, as it is associated with the presence of a number of histocompatibility genes of the first and second classes, for example, HLA-DR4 and HLA-DR3. Individuals with both -DR4 and -DR3 antigens are most at risk of developing IDDM. The proportion of patients with IDDM is 15-20% of the total.

2. Non-insulin-dependent diabetes mellitus - NIDDM (DM-II). This form of diabetes is called adult diabetes because it usually starts after the age of 40.

The development of this type of DM is not associated with the human major histocompatibility system. Patients with this type of diabetes have a normal or moderately reduced number of insulin-producing cells in the pancreas, and it is now believed that NIDDM develops as a result of a combination of insulin resistance and a functional impairment in the ability of the patient's b-cells to secrete a compensatory amount of insulin. The proportion of patients with this form of diabetes is 80-85%.

In addition to the two main types, there are:

3. DM associated with malnutrition.

4. Secondary, symptomatic diabetes (endocrine origin: goiter, acromegaly, pancreatic disease).

5. Pregnancy diabetes.

Currently, there is a certain methodology, that is, a system of principles and views on the treatment of patients with diabetes, the key of which are:

1) compensation for insulin deficiency;

2) correction of hormonal and metabolic disorders;

3) correction and prevention of early and late complications.

According to the latest principles of treatment, the following three traditional components remain the main methods of therapy for patients with diabetes:

2) insulin preparations for patients with IDDM;

3) hypoglycemic oral agents for patients with NIDDM.

In addition, it is important to comply with the regimen and degree of physical activity. Among the pharmacological agents used to treat patients with diabetes, there are two main groups of drugs:

I. Insulin preparations.

II. Synthetic oral (tablet) antidiabetic agents.

Parathyroidin- the drug of the parathyroid hormone parathyrin (parathormone), has recently been used very rarely, since there are more effective means. The regulation of the production of this hormone depends on the amount of Ca 2+ in the blood. The pituitary gland does not affect the synthesis of parathyrin.

Pharmacological is to regulate the exchange of calcium and phosphorus. Its target organs are bones and kidneys, which have specific membrane receptors for parathyrin. In the intestine, parathyrin activates the absorption of calcium and inorganic phosphate. It is believed that the stimulating effect on calcium absorption in the intestine is not associated with the direct influence of parathyrin, but with an increase in formation under its influence. calcitriol (active form of calciferol in the kidneys). In the renal tubules, parathyrin increases calcium reabsorption and decreases phosphate reabsorption. At the same time, in accordance with the content of phosphorus in the blood decreases, while the level of calcium increases.

Normal levels of parathyrin have an anabolic (osteoplastic) effect with increased bone growth and mineralization. With hyperfunction of the parathyroid glands, osteoporosis occurs, hyperplasia of fibrous tissue, which leads to deformation of the bones, their fractures. In cases of overproduction of parathyrin, calcitonin which prevents calcium from being washed out of the bone tissue.

Indications: hypoparathyroidism, to prevent tetany due to hypocalcemia (in acute cases, intravenous calcium preparations or their combination with parathyroid hormone preparations should be administered).

Contraindications: increased calcium in the blood, with diseases of the heart, kidneys, allergic diathesis.

Dihydrotachysterol (takhistin) - chemically close to ergocalciferol (vitamin D2). Increases the absorption of calcium in the intestines, at the same time - the excretion of phosphorus in the urine. Unlike ergocalciferol, there is no D-vitamin activity.

Indications: disorders of phosphorus-calcium metabolism, including hypocalcic convulsions, spasmophilia, allergic reactions, hypoparathyroidism.

Contraindications: increased calcium in the blood.

Side effect: nausea.

Hormonal preparations of the pancreas.

insulin preparations

In the regulation of metabolic processes in the body, pancreatic hormones are of great importance. IN β-cells pancreatic islets are synthesized insulin, which has a pronounced hypoglycemic effect, in a-cells produced contrainsular hormone glucagon, which has a hyperglycemic effect. Besides, δ-clitite pancreas produce somatostatin .

Insufficient insulin secretion leads to diabetes mellitus (DM). diabetes mellitus - a disease that occupies one of the dramatic pages of world medicine. According to WHO, the number of patients with diabetes worldwide in 2000 was 151 million people by 2010 is expected to increase to 221 million people, and by 2025 - 330 million people, which suggests its global epidemic. DM causes the earliest of all diseases disability, high mortality, frequent blindness, kidney failure, and is also a risk factor for cardiovascular disease. Diabetes ranks first among endocrine diseases. The United Nations has declared SD a pandemic of the 21st century.

According to the WHO classification (1999.) There are two main types of the disease - type 1 and type 2 diabetes(according to insulin-dependent and non-insulin-dependent diabetes). Moreover, an increase in the number of patients is predicted mainly due to patients with type 2 diabetes, which currently account for 85-90% of the total number of patients with diabetes. This type of DM is diagnosed 10 times more often than type 1 DM.

Diabetes is treated with diet, insulin preparations, and oral antidiabetic drugs. Effective treatment of patients with CD should provide approximately the same basal insulin level throughout the day and prevent hyperglycemia that occurs after eating (postprandial glycemia).

The main and only objective indicator of the effectiveness of DM therapy, reflecting the state of compensation for the disease, is the level of glycated hemoglobin (HbA1C or A1C). HbA1c or A1C - hemoglobin, which is covalently linked to glucose and is an indicator of the level of glycemia for the previous 2-3 months. Its level correlates well with the values of blood glucose levels and the likelihood of complications of diabetes. A 1% decrease in glycosylated hemoglobin is accompanied by a 35% decrease in the risk of developing complications of diabetes (regardless of the initial level of HbA1c).

The basis of the treatment of CD is properly selected hypoglycemic therapy.

Historical reference. The principles for obtaining insulin were developed by L. V. Sobolev (in 1901), who, in an experiment on the glands of newborn calves (they still do not have trypsin, decomposes insulin), showed that the pancreatic islets (Langerhans) are the substrate of the internal secretion of the pancreas. In 1921, Canadian scientists F. G. Banting and C. X. Best isolated pure insulin and developed a method for industrial production. After 33 years, Sanger and his co-workers deciphered the primary structure of bovine insulin, for which they received the Nobel Prize.

The creation of insulin preparations took place in several stages:

First generation insulins - porcine and bovine (bovine) insulin;

Second generation insulins - monopic and monocomponent insulins (50s of the XX century)

Third generation insulins - semi-synthetic and genetically engineered insulin (80s of the XX century)

Obtaining insulin analogs and inhaled insulin (late XX - early XXI century).

Animal insulins differed from human insulin in amino acid composition: bovine insulin - in amino acids in three positions, pork - in one position (position 30 in chain B). Immunological adverse reactions occurred more frequently with bovine insulin than with porcine or human insulin. These reactions were expressed in the development of immunological resistance and allergy to insulin.

To reduce the immunological properties of insulin preparations, special purification methods have been developed, which made it possible to obtain a second generation. First there were monopeak insulins obtained by gel chromatography. Later it was found that they contain a small amount of impurities of insulin-like peptides. The next step was the creation of monocomponent insulins (UA-insulins), which were obtained by additional purification using ion exchange chromatography. With the use of monocomponent porcine insulins, the production of antibodies and the development of local reactions in patients were rare (now bovine and monopic porcine insulins are not used in Ukraine).

Human insulin preparations are obtained either by a semi-synthetic method using an enzymatic-chemical substitution at position B30 in porcine insulin of the amino acid alanine for threonine, or by a biosynthetic method using genetic engineering technology. Practice has shown that there is no significant clinical difference between human insulin and high-quality monocomponent porcine insulin.

Now work continues on improving and searching for new forms of insulin.

According to the chemical structure, insulin is a protein, the molecule of which consists of 51 amino acids, forming two polypeptide chains connected by two disulfide bridges. In the physiological regulation of insulin synthesis, the dominant role is played by the concentration glucose in blood. Penetrating into β-cells, glucose is metabolized and contributes to an increase in the intracellular ATP content. The latter, by blocking ATP-dependent potassium channels, causes depolarization of the cell membrane. This facilitates the penetration of calcium ions into β-cells (through voltage-gated calcium channels that have opened) and the release of insulin by exocytosis. In addition, insulin secretion is affected by amino acids, free fatty acids, glucagon, secretin, electrolytes (especially Ca 2+), the autonomic nervous system (the sympathetic nervous system is inhibitory, and the parasympathetic nervous system is stimulating).

Pharmacodynamics. The action of insulin is aimed at the metabolism of carbohydrates, proteins, fats, minerals. The main thing in the action of insulin is its regulatory effect on the metabolism of carbohydrates, lowering the content of glucose in the blood. This is achieved by the fact that insulin promotes the active transport of glucose and other hexoses, as well as pentoses through cell membranes and their utilization by the liver, muscle and adipose tissues. Insulin stimulates glycolysis, induces the synthesis of the enzymes glucokinase, phosphofructokinase and pyruvate kinase, stimulates the pentose phosphate cycle by activating glucose-6-phosphate dehydrogenase, increases glycogen synthesis by activating glycogen synthetase, the activity of which is reduced in patients with diabetes. On the other hand, the hormone inhibits glycogenolysis (decomposition of glycogen) and gluconeogenesis.

Insulin plays an important role in stimulating nucleotide biosynthesis, increasing the content of 3,5 nucleotases, nucleoside triphosphatase, including in the nuclear envelope, where it regulates the transport of mRNA from the nucleus to the cytoplasm. Insulin stimulates the biosynthesis of nucleic acids and proteins. In parallel to the enhancement of anabolic processes, insulin inhibits the catabolic reactions of the breakdown of protein molecules. It also stimulates the processes of lipogenesis, the formation of glycerol, its introduction into lipids. Along with the synthesis of triglycerides, insulin activates the synthesis of phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin) in fat cells, and also stimulates the biosynthesis of cholesterol, which, like phospholipids and some glycoproteins, is necessary for building cell membranes.

With an insufficient amount of insulin, lipogenesis is suppressed, lipogenesis increases, lipid peroxidation in the blood and urine increases the level of ketone bodies. Due to the reduced activity of lipoprotein lipase in the blood, the concentration of β-lipoproteins, which are essential in the development of atherosclerosis, increases. Insulin prevents the body from losing fluid and K+ in the urine.

The essence of the molecular mechanism of action of insulin on intracellular processes is not fully disclosed. However, the first step in the action of insulin is binding to specific receptors on the plasma membrane of target cells, primarily in the liver, adipose tissue and muscles.

Insulin binds to the α-subunit of the receptor (contains the main insulin-binding domain). At the same time, the kinase activity of the β-subunit of the receptor (Tyrosine kinase) is stimulated, it is autophosphorylated. An "insulin + receptor" complex is created, which penetrates into the cell by endocytosis, where insulin is released and the cellular mechanisms of the hormone's action are triggered.

In the cellular mechanisms of insulin action, not only secondary messengers take part: cAMP, Ca 2+, calcium-calmodulin complex, inositol triphosphate, diacylglycerol, but also fructose-2,6-diphosphate, which is called the third mediator of insulin in its effect on intracellular biochemical processes. It is the growth under the influence of insulin of the level of fructose-2,6-diphosphate that promotes the utilization of glucose from the blood, the formation of fats from it.

The number of receptors and their ability to bind is influenced by a number of factors. In particular, the number of receptors is reduced in cases of obesity, non-insulin dependent type 2 diabetes, and peripheral hyperinsulinism.

Insulin receptors exist not only on the plasma membrane, but also in the membrane components of such internal organelles as the nucleus, endoplasmic reticulum, Golgi complex. The introduction of insulin to patients with diabetes helps to reduce the level of glucose in the blood and the accumulation of glycogen in tissues, reduce glucosuria and associated polyuria, polydipsia.

Due to the normalization of protein metabolism, the concentration of nitrogen compounds in the urine decreases, and as a result of the normalization of fat metabolism, ketone bodies - acetone, acetoacetic and hydroxybutyric acids - disappear from the blood and urine. Weight loss stops and excessive feeling of hunger disappears ( bulimia ). The detoxification function of the liver increases, the body's resistance to infections increases.

Classification. Modern insulin preparations differ from each other speed And duration of action. They can be divided into the following groups:

1. Short-acting insulin preparations, or simple insulins ( actrapid MK , humulin etc.) The decrease in blood glucose levels after their subcutaneous injection begins after 15-30 minutes, the maximum effect is observed after 1.5-3 hours, the effect lasts 6-8 hours.

Significant advances in the study of molecular structure, biological activity and therapeutic properties have led to the modification of the human insulin formula and the development of short-acting insulin analogues.

The first analogue lisproinsulin (humalog) is identical to human insulin except for the position of lysine and proline at positions 28 and 29 of the B chain. Such a change did not affect the activity of the A-chain, but reduced the processes of self-association of insulin molecules and ensured an acceleration of absorption from the subcutaneous depot. After the injection, the onset of action is after 5-15 minutes, reaching a peak after 30-90 minutes, the duration of action is 3-4 hours.

The second analogue aspart(tradename - novo-rapid) modified by replacing one amino acid in position B-28 (proline) with aspartic acid, reduces the phenomenon of cell self-aggregation of insulin molecules into dimmers and hexamers and accelerates its absorption.

The third analogue - glulisin(tradename epaidra) is practically similar to endogenous human insulin and biosynthetic regular human insulin with certain structural changes in the formula. Thus, in the 33 position, asparagine is replaced by lysine, and the lysine in position B29 is replaced by glutamic acid. By stimulating the peripheral use of glucose by skeletal muscles and adipose tissue, inhibiting gluconeogenesis in the liver, glulisin (epidra) improves glycemic control, also inhibits lipolysis and proteolysis, accelerates protein synthesis, activates insulin receptors and its substrates, and is fully consistent with the effect of regular human insulin on these elements.

2. Long-acting insulin preparations:

2.1. medium duration (The onset of action after subcutaneous administration is 1.5-2 hours, duration 8-12 hours). These drugs are also called insulin semilente. This group includes insulins on neutral Protamine Hagedorn: B-insulin, Monodar B, Farmasulin HNP. Since insulin and protamine are included in HNP-insulin in equal, isophaneous, ratios, they are also called isophane insulins;

2.2. Long acting (ultralente) with onset of action after 6-8 hours, duration of action 20-30 hours. These include insulin preparations containing Zn2 + in their composition: suspension-insulin-ultralente, Farmasulin HL. Long-acting drugs are administered only subcutaneously or intramuscularly.

3. Combined preparations containing standard mixtures of group 1 drugs with NPH-insulins in different ratios of groups 1 and 2: 30/70, 20/80,10/90, etc. - Monodar K ZO, Farmasulin 30/70 m. Some drugs are available in special syringe tubes.

To achieve maximum glycemic control in diabetic patients, an insulin regimen is needed that fully mimics the physiological profile of insulin during the day. Long-acting insulins have their drawbacks, in particular, the presence of a peak effect 5-7 hours after the administration of the drug leads to the development of hypoglycemia, especially at night. These shortcomings have led to the development of insulin analogues with pharmacokinetic properties of effective basic insulin therapy.

One of these drugs created by Aventis - insulin glargine (Lantus), which differs from the human in three amino acid residues. Glargine Sulin is a stable insulin structure, completely soluble at pH 4.0. The drug does not dissolve in the subcutaneous tissue, which has a pH of 7.4, which leads to the formation of microprecipitates at the injection site and its slow release into the bloodstream. The absorption is slowed down by the addition of a small amount of zinc (30 µg/ml). Slowly absorbed, glargine-insulin does not have a peak effect and provides almost basal insulin concentration during the day.

New promising insulin preparations are being developed - inhaled insulin (creation of an insulin-air mixture for inhalation) oral insulin (spray for the oral cavity); buccal insulin (in the form of drops for the oral cavity).

A new method of insulin therapy is the introduction of insulin using an insulin pump, which provides a more physiological way of administering the drug, the absence of insulin depot in the subcutaneous tissue.

The activity of insulin preparations is determined by the method of biological standardization and is expressed in units. 1 unit corresponds to the activity of 0.04082 mg of crystalline insulin. The dose of insulin for each patient is selected individually in a hospital with constant monitoring of the level of HbA1c in the blood and the sugar content in the blood and urine after the administration of the drug. When calculating the daily dose of insulin, it should be taken into account that 1 IU of insulin promotes the absorption of 4-5 g of sugar excreted in the urine. The patient is transferred to a diet with a limited amount of easily digestible carbohydrates.

Simple insulins are administered 30-45 minutes before meals. Intermediate-acting insulins are usually taken twice (half an hour before breakfast and at 18.00 before dinner). Long-acting drugs are administered together with simple insulins in the morning.

Two main variants of insulin therapy are used: traditional and intensive.

Traditional insulin therapy- this is the appointment of standard mixtures of short-acting insulin and NPH-insulin 2/3 of the dose before breakfast, 1/3 before dinner. However, with this type of therapy, hyperinsulinemia occurs, which requires 5-6 meals during the day, hypoglycemia may develop, and a high frequency of late complications of diabetes.

Intensive (basic-bolus) insulin therapy- this is the use of twice a day insulin of medium duration of action (to create a basal level of the hormone) and the additional introduction of short-acting insulin before breakfast, lunch and dinner (imitation of bolus physiological secretion of insulin in response to meals). With this type of therapy, the patient himself selects the dose of insulin based on measuring the level of glycemia using a glucometer.

Indications: insulin therapy is absolutely indicated in patients with type 1 diabetes. It should be started in those patients in whom diet, normalization of body weight, physical activity and oral antidiabetic drugs do not provide the desired effect. Simple insulin is used for diabetic coma, as well as for diabetes of any type, if it is accompanied by complications: ketoacidosis, infection, gangrene, heart disease, liver, surgery, postoperative period; to improve the nutrition of patients exhausted by a long illness; as part of a polarizing mixture for heart diseases.

Contraindications: diseases with hypoglycemia, hepatitis, liver cirrhosis, pancreatitis, glomerulonephritis, nephrolithiasis, peptic ulcer of the stomach and duodenum, decompensated heart disease; for long-acting drugs - coma, infectious diseases, during the surgical treatment of patients with diabetes.

Side effect soreness of injections, local inflammatory reactions (infiltrates), allergic reactions, the emergence of resistance to the drug, the development of lipodystrophy.

Insulin overdose can cause hypoglycemia. Symptoms of hypoglycemia: anxiety, general weakness, cold sweat, trembling of the limbs. A significant decrease in blood sugar leads to impaired brain function, the development of coma, seizures and even death. Patients with diabetes should have a few pieces of sugar with them to prevent hypoglycemia. If, after taking sugar, the symptoms of hypoglycemia do not disappear, you need to urgently inject 20-40 ml of a 40% glucose solution intravenously, 0.5 ml of a 0.1% adrenaline solution can be injected subcutaneously. In cases of significant hypoglycemia due to the action of long-acting insulin preparations, patients are more difficult to withdraw from this state than from hypoglycemia caused by short-acting insulin preparations. The presence of a long-acting protamine protein in some preparations explains the frequent cases of allergic reactions. However, injections of long-acting insulin preparations are less painful due to the higher pH of these preparations.

The pancreas is the most important digestive gland, producing a large number of enzymes that perform the absorption of proteins, lipids, carbohydrates. It is also a gland that synthesizes insulin and one of the inhibitory hormones - glucagon. When the pancreas does not cope with its functions, it is necessary to take pancreatic hormone preparations. What are the indications and contraindications for taking these drugs.

The pancreas is an important digestive organ.

- This is an elongated organ, located closer to the back of the abdominal cavity and slightly extending to the area of \u200b\u200bthe left side of the hypochondrium. The organ includes three parts: head, body, tail.

Large in volume and extremely necessary for the activity of the body, iron performs external and intrasecretory work.

Its exocrine region has classic secretory sections, a ductal part, where the formation of pancreatic juice is carried out, which is necessary for the digestion of food, the decomposition of proteins, lipids, and carbohydrates.

The endocrine region includes the pancreatic islets, which are responsible for the synthesis of hormones and the control of carbohydrate-lipid metabolism in the body.

An adult normally has a head of the pancreas with a size of 5 cm or more, in thickness this area is within 1.5-3 cm. The width of the body of the gland is approximately 1.7-2.5 cm. The tail part can be up to 3, 5 cm, and in width up to one and a half centimeters.

The entire pancreas is covered with a thin capsule of connective tissue.

According to its mass, the pancreatic gland of an adult is in the range of 70-80 g.

Pancreatic hormones and their functions

The organ performs external and intrasecretory work

The two main hormones of the body are insulin and glucagon. They are responsible for lowering and raising blood sugar levels.

The production of insulin is carried out by β-cells of the islets of Langerhans, which are concentrated mainly in the tail of the gland. Insulin is responsible for getting glucose into cells, stimulating its uptake and lowering blood sugar levels.

The hormone glucagon, on the contrary, raises the amount of glucose, stopping hypoglycemia. The hormone is synthesized by α-cells that make up the islets of Langerhans.

An interesting fact: alpha cells are also responsible for the synthesis of lipocaine, a substance that prevents the appearance of fatty deposits in the liver.

In addition to alpha and beta cells, the islets of Langerhans are approximately 1% delta cells and 6% PP cells. Delta cells produce ghrelin, the appetite hormone. PP cells synthesize a pancreatic polypeptide that stabilizes the secretory function of the gland.

The pancreas produces hormones. All of them are necessary to sustain human life. Further on the hormones of the gland in more detail.

Insulin

Insulin in the human body is produced by special cells (beta cells) of the pancreatic gland. These cells are located in a large volume in the tail part of the organ and are called the islets of Langerhans.

Insulin controls blood glucose levels

Insulin is primarily responsible for controlling blood glucose levels. This process is done like this:

with the help of a hormone, the permeability of the cell membrane is stabilized, and glucose easily penetrates through it;
insulin plays a role in performing the transition of glucose to glycogen storage in muscle tissue and the liver;
the hormone helps in the breakdown of sugar;
inhibits the activity of enzymes that break down glycogen, fat.

A decrease in the production of insulin by the body's own forces leads to the formation of type I diabetes mellitus in a person. In this process, without the possibility of recovery, beta cells are destroyed, in which insulin is healthy during carbohydrate metabolism. Patients with this type of diabetes need regular administration of manufactured insulin.

If the hormone is produced in the optimal volume, and the cell receptors lose sensitivity to it, this signals the formation of type 2 diabetes mellitus. Insulin therapy is not used in the initial stages of this disease. With an increase in the severity of the disease, the endocrinologist prescribes insulin therapy to reduce the level of load on the organ.

Glucagon

Glucagon - breaks down glycogen in the liver

The peptide is formed by A-cells of the islets of the organ and cells of the upper part of the digestive tract. The production of glucagon is stopped due to an increase in the level of free calcium inside the cell, which can be observed, for example, when exposed to glucose.

Glucagon is the main antagonist of insulin, which is especially pronounced when there is a lack of the latter.

Glucagon affects the liver, where it promotes the breakdown of glycogen, causing an accelerated increase in the concentration of sugar in the bloodstream. Under the influence of the hormone, the breakdown of proteins and fats is stimulated, and the production of proteins and lipids is stopped.

Somatostatin

The polypeptide produced in the D-cells of the islets is characterized by the fact that it reduces the synthesis of insulin, glucagon, and growth hormone.

Vasointense peptide

The hormone is produced by a small number of D1 cells. Vasoactive intestinal polypeptide (VIP) is built using more than twenty amino acids. Normally, the body is in the small intestine and organs of the peripheral and central nervous system.

VIP features:

increases blood flow activity in, activates motility;
reduces the rate of release of hydrochloric acid by parietal cells;
starts the production of pepsinogen - an enzyme that is a component of gastric juice and breaks down proteins.

Due to the increase in the number of D1-cells synthesizing the intestinal polypeptide, a hormonal tumor is formed in the organ. Such a neoplasm in 50% of cases is oncological.

Pancreatic polypeptide

Mountain stabilizing the activity of the body, will stop the activity of the pancreas and activate the synthesis of gastric juice. If the structure of the organ has a defect, the polypeptide will not be produced in the proper amount.

Amylin

Describing the functions and effects of amylin on organs and systems, it is important to pay attention to the following:

the hormone prevents excess glucose from entering the blood;
reduces appetite, contributing to the feeling of satiety, reduces the size of the portion of food consumed;
maintains the secretion of the optimal ratio of digestive enzymes that work to reduce the rate of increase in glucose levels in the bloodstream.

In addition, amylin slows down the production of glucagon during meals.

Lipocaine, kallikrein, vagotonin

Lipocaine triggers the metabolism of phospholipids and the combination of fatty acids with oxygen in the liver. The substance increases the activity of lipotropic compounds in order to prevent fatty degeneration of the liver.

Kallikrein, although produced in the gland, is not activated in the body. When the substance passes into the duodenum, it is activated and acts: it lowers blood pressure and blood sugar levels.

Vagotonin promotes the formation of blood cells, lowering the amount of glucose in the blood, as it slows down the decomposition of glycogen in the liver and muscle tissue.

centropnein and gastrin

Gastrin is synthesized by the cells of the gland and the gastric mucosa. It is a hormone-like substance that increases the acidity of the digestive juice, triggers the synthesis of pepsin, and stabilizes the course of digestion.

Centropnein is a protein substance that activates the respiratory center and increases the diameter of the bronchi. Centropnein promotes the interaction of iron-containing protein and oxygen.

Gastrin

Gastrin promotes the formation of hydrochloric acid, increases the amount of synthesis of pepsin by the cells of the stomach. This is well reflected in the course of the activity of the gastrointestinal tract.

Gastrin may reduce the rate of emptying. With the help of this, the effect of hydrochloric acid and pepsin on the food mass should be ensured in time.

Gastrini has the ability to regulate carbohydrate metabolism, activate the growth of production of secretin and a number of other hormones.

Hormone preparations

Pancreatic hormone preparations have traditionally been described for the purpose of reviewing the treatment regimen for diabetes mellitus.

The problem of pathology is a violation in the ability of glucose to enter the cells of the body. As a result, there is an excess of sugar in the bloodstream, and an extremely acute deficiency of this substance occurs in the cells.

There is a serious failure in the energy supply of cells and metabolic processes. Treatment with drugs has the main goal - to stop the described problem.

Classification of antidiabetic agents

Insulin preparations are prescribed by the doctor individually for each patient.

Insulin medicines:

monosuinsulin;
suspension of Insulin-semilong;
suspension of Insulin-long;
Suspension of insulin-ultralong.

The dosage of the listed drugs is measured in units. The calculation of the dose is based on the concentration of glucose in the bloodstream, taking into account the fact that 1 unit of the drug stimulates the removal of 4 g of glucose from the blood.

Supfonyl urea derivatives:

tolbutamide (Butamid);
chlorpropamide;
glibenclamide (Maninil);
gliclazide (Diabeton);
glipizide.

Impact principle:

inhibit ATP-dependent potassium channels in pancreatic beta cells;
depolarization of the membranes of these cells;
triggering potential-dependent ion channels;
penetration of calcium into the cell;
calcium increases the release of insulin into the bloodstream.

Biguanide derivatives:

Metformin (Siofor)

Tablets Diabeton

The principle of action: increases the capture of sugar by the cells of the skeletal muscle tissue and increases its anaerobic glycolysis.

The drug reduces the resistance of cells to the hormone: pioglitazone.

Mechanism of action: at the DNA level, it increases the production of proteins that increase the perception of the hormone by tissues.

Acarbose

Mechanism of action: reduces the amount of glucose absorbed by the intestines, which enters the body with food.

Until recently, the treatment of patients with diabetes used drugs derived from animal hormones or from modified animal insulin, in which a single amino acid change was made.

Progress in the development of the pharmaceutical industry has led to the ability to develop drugs with a high level of quality using genetic engineering tools. The insulins obtained by this method are hypoallergenic; a smaller dose of the drug is used to effectively suppress the signs of diabetes.

How to take drugs correctly

There are a number of rules that are important to observe at the time of taking the drugs:

The drug is prescribed by a doctor, indicates the individual dosage and duration of therapy.
For the period of treatment, it is recommended to follow a diet: exclude alcoholic beverages, fatty foods, fried foods, sweet confectionery.
It is important to check that the prescribed medicine has the same dosage as indicated in the prescription. It is forbidden to divide the pills, as well as to increase the dosage with your own hands.
In the event of side effects or the absence of a result, it is necessary to notify the doctor.

Contraindications and side effects

In medicine, human insulins, developed by genetic engineering, and highly purified porcine insulins are used. In view of this, side effects of insulin therapy are observed relatively infrequently.

Allergic reactions, pathologies of adipose tissue at the injection site are likely.

When excessively high doses of insulin enter the body or with limited administration of alimentary carbohydrates, increased hypoglycemia may occur. Its severe variant is a hypoglycemic coma with loss of consciousness, convulsions, insufficiency in the work of the heart and blood vessels, and vascular insufficiency.

Symptoms of hypoglycemia

During this state, the patient must be injected intravenously with a 40% glucose solution in the amount of 20-40 (not more than 100) ml.

Since hormone preparations are used until the end of life, it is important to remember that their hypoglycemic potential can be deformed by various medications.

Increase the hypoglycemic effect of the hormone: alpha-blockers, P-blockers, antibiotics of the tetracycline group, salicylates, parasympatholytic medicinal substance, drugs that mimic testosterone and dihydrotestosterone, antimicrobial agents sulfonamides.

Major pancreatic hormones:

Insulin (normal concentration in the blood in a healthy person is 3-25 mcU / ml, in children 3-20 mcU / ml, in pregnant women and the elderly 6-27 mcU / ml);

glucagon (plasma concentration 27-120 pg/ml);

c-peptide (normal level 0.5-3.0 ng/ml);

· pancreatic polypeptide (the level of PP in fasting serum is 80 pg/ml);

gastrin (norm from 0 to 200 pg / ml in blood serum);

amylin;

The main function of insulin in the body is to lower blood sugar levels. This happens due to the simultaneous action in several directions. Insulin stops the formation of glucose in the liver, increasing the amount of sugar absorbed by the tissues of our body due to the permeability of cell membranes. And at the same time, this hormone stops the breakdown of glucagon, which is part of a polymer chain consisting of glucose molecules.

The alpha cells of the islets of Langerhans are responsible for the production of glucagon. Glucagon is responsible for increasing the amount of glucose in the bloodstream by stimulating its formation in the liver. In addition, glucagon promotes the breakdown of lipids in adipose tissue.

A growth hormone growth hormone increases the activity of alpha cells. In contrast, the delta cell hormone somatostatin inhibits the formation and secretion of glucagon, as it blocks the entry into alpha cells of Ca ions, which are necessary for the formation and secretion of glucagon.

Physiological significance lipocaine. It promotes the utilization of fats by stimulating the formation of lipids and the oxidation of fatty acids in the liver, it prevents fatty degeneration of the liver.

Functions vagotonin- increased tone of the vagus nerves, increased their activity.

Functions centropnein- excitation of the respiratory center, promoting relaxation of the smooth muscles of the bronchi, increasing the ability of hemoglobin to bind oxygen, improving oxygen transport.

The human pancreas, mainly in its caudal part, contains approximately 2 million islets of Langerhans, which make up 1% of its mass. The islets are made up of alpha, beta, and delta cells that secrete glucagon, insulin, and somatostatin (which inhibit growth hormone secretion), respectively.

Insulin Normally, it is the main regulator of blood glucose levels. Even a slight increase in blood glucose causes the secretion of insulin and stimulates its further synthesis by beta cells.

CLASSIFICATION OF INSULIN DRUGS

All insulin preparations manufactured by global pharmaceutical companies differ mainly in three main features:

1) by origin;

2) by the speed of onset of effects and their duration;

3) according to the method of purification and the degree of purity of preparations.

I. By origin, they distinguish:

a) natural (biosynthetic), natural, insulin preparations made from the pancreas of cattle, for example, insulin tape GPP, ultralente MS, and more often pigs (for example, actrapid, insulrap SPP, monotard MS, semilente, etc.);

b) synthetic or, more precisely, species-specific, human insulins. These drugs are obtained using genetic engineering methods by DNA recombinant technology, and therefore they are most often called DNA recombinant insulin preparations (actrapid NM, homofan, isophane NM, humulin, ultratard NM, monotard NM, etc.).

III. According to the speed of onset of effects and their duration, there are:

a) quick short-acting drugs (actrapid, actrapid MS, actrapid NM, insulrap, homorap 40, insuman rapid, etc.). The onset of action of these drugs is after 15-30 minutes, the duration of action is 6-8 hours;

b) drugs of medium duration of action (onset of action after 1-2 hours, the total duration of the effect is 12-16 hours); - Semilente MS; - humulin N, humulin tape, homofan; - tape, tape MC, monotard MC (2-4 hours and 20-24 hours, respectively); - iletin I NPH, iletin II NPH; - insulong SPP, insulin tape GPP, SPP, etc.

c) drugs of medium duration mixed with short-acting insulin: (onset of action 30 minutes; duration - from 10 to 24 hours);

Aktrafan NM;

Humulin M-1; M-2; M-3; M-4 (duration of action up to 12-16 hours);

Insuman comb. 15/85; 25/75; 50/50 (valid for 10-16 hours).

d) long-acting drugs:

Ultratape, ultratape MS, ultratape HM (up to 28 hours);

Insulin Superlente SPP (up to 28 hours);

Humulin ultralente, ultratard HM (up to 24-28 hours).

Actrapid, derived from the beta cells of the porcine pancreatic islets, is available as an official drug in 10 ml vials, most often with an activity of 40 IU per 1 ml. It is administered parenterally, most often under the skin. This drug has a rapid hypoglycemic effect. The effect develops after 15-20 minutes, and the peak of action is noted after 2-4 hours. The total duration of the hypoglycemic effect is 6-8 hours in adults, and in children up to 8-10 hours.

Advantages of fast short-acting insulin preparations (Actrapida):

1) act quickly;

2) give a physiological peak in blood concentration;

3) are short-lived.

Indications for the use of rapid short-acting insulin preparations:

1. Treatment of patients with insulin-dependent diabetes mellitus. The drug is injected under the skin.

2. In the most severe forms of non-insulin dependent diabetes mellitus in adults.

3. With diabetic (hyperglycemic) coma. In this case, the drugs are administered both under the skin and into a vein.

ANTI-DIABETIC (HYPOGLYCEMIC) ORAL MEDICINES

Stimulating the secretion of endogenous insulin (sulfonylurea drugs):

1. First generation drugs:

a) chlorpropamide (syn.: diabinez, katanil, etc.);

b) bukarban (syn.: oranil, etc.);

c) butamide (syn.: orabet, etc.);

d) tolinase.

2. Second generation drugs:

a) glibenclamide (syn.: maninil, oramide, etc.);

b) glipizide (syn.: minidiab, glibinez);

c) gliquidone (syn.: glurenorm);

d) gliclazide (synonym: predian, diabeton).

II. Influencing the metabolism and absorption of glucose (biguanides):

a) buformin (glibutide, adebit, silbine retard, dimethyl biguanide);

b) metformin (gliformin). III. Inhibiting glucose absorption:

a) glucobay (acarbose);

b) guarem (guar gum).

BUTAMIDE (Butamidum; issue in tab. 0.25 and 0.5) is a first-generation drug, a sulfonylurea derivative. The mechanism of its action is associated with a stimulating effect on pancreatic beta cells and their increased secretion of insulin. The onset of action is 30 minutes, its duration is 12 hours. Assign the drug 1-2 times a day. Butamide is excreted by the kidneys. This drug is well tolerated.

Side effects:

1. Dyspepsia. 2. Allergy. 3. Leukocytopenia, thrombocytopenia. 4. Hepatotoxicity. 5. Development of tolerance is possible.

BIGUANIDES are derivatives of guanidine. The two best known are:

Buformin (glibutide, adebite);

Metformin.

GLIBUTID (Glibutidum; issue in tab. 0.05)

1) promotes the absorption of glucose by muscles in which lactic acid accumulates; 2) increases lipolysis; 3) reduces appetite and body weight; 4) normalizes protein metabolism (in this regard, the drug is prescribed for overweight).

Most often they are used in patients with DM-II, accompanied by obesity.