Endocrine physiology

2021-06-16 03:16 PM

Insulin is composed of two polypeptide chains, connected by disulphide bridges, with 51 amino acids, molecular weight 5808.

Recalling anatomy and organization

The pancreas is in the duodenum, behind the stomach. Weight 70-80g. 10-18cm long, 6cm high, 1-3cm thick. The endocrine pancreas is composed of islets of Langerhans (consisting of 1-2 million islands), which are cells clustered in clusters, occupying 1 g of pancreatic tissue, usually located near blood vessels, emptying into the portal vein. The pancreatic nerve is a branch of the X nerve.

 

Figure: Microscopic view of an islet.

Each islet consists of four cell types, which are distinguished by their structure, morphology, and staining properties (Fig.

Alpha cells secrete glucagon causing hyperglycaemia (20%).

Beta cells secrete insulin causing hypoglycaemia (60-75%).

Somatostatin-secreting delta cells regulate insulin and glucagon secretion (5%).

PP cells secrete a hormone of unknown function called a pancreatic polypeptide.

Pancreatic hormones

Insulin

Chemical structure:

Insulin is composed of two polypeptide chains, connected by disulphide bridges, with 51 amino acids, molecular weight 5808. When these two chains separate, the activity will be lost.

Insulin is synthesized from beta cells in the endoplasmic reticulum via two precursors, preproinsulin, to proinsulin. Proinsulin splits into insulin and C peptide in the golgi reticulum. However, about 1/6 is still in the form of proinsulin and is not biologically active.

Mechanism of insulin secretion via cyclic AMP.

Insulin transport and degradation:

In the blood, insulin is completely free and has a half-life of 6 minutes and is eliminated from the blood after 10-15 minutes. Except for the amount of insulin that binds to the receptor in the target cell, the remaining insulin is broken down by insulins in the liver, kidney, muscle, and other tissues. The fasting insulin concentration in Vietnamese is 0.178 (0.077 mmol/l.

Function:

Glucose metabolism: causes hypoglycaemia in 2 ways.

Increased utilization: increased glycogen synthesis in the liver, increased muscle glycogen stores, increased intestinal glucose breakdown, increased glucose conversion to fatty acids.

Decrease sugar production: reduce glucose production from glycogen, reduce new sugar from protein.

Mechanism of action:

Inhibiting the effect of GH on hexokinase and inhibiting phosphatase leads to a decrease in the breakdown of glycogen to glucose.

Increases cell permeability to glucose by insulin.

Insulin increases the amount of glycogen in the liver, which can be stored in the liver up to 100 grams. When too much glucose is taken into the liver, the excess glucose is converted into fatty acids and transferred to adipose tissue for storage.

Protein metabolism: increase protein synthesis, increase transport of a.amine into cells, stimulate growth. Lack of insulin increased protein degradation. Together with the GH of the yen makes the body grow.

Lipid metabolism: increase fat accumulation, stimulate fat synthesis in the liver and adipose tissue, increase fatty acid synthesis from glucose in the liver.

Without insulin, the above effects are reversed, the uptake of glucose and amino acids into the cells is reduced; increased glycogen, lipid and protein degradation, causing hyperglycaemia; reduce the use of triglycerides for energy. The brain and liver alone are not affected because they are insulin-independent.

Glucose ingested 50% oxidized for energy; 5% glycogen stores; 30-40% of stored fat (triglycerides). If there is a lack of insulin, only 5% is converted to stored fat, oxidation decreases, glycogen decreases; blood glucose is elevated.

Regulate secretions:

The rate of insulin release, as well as its concentration in the plasma, is mainly controlled by high blood glucose levels, causing increased insulin secretion and vice versa.

Digestive hormones such as secretin, gastrin... stimulate insulin secretion.

 In addition, the X cord also stimulates the beta cells to secrete insulin.

Glucagon

Nature is a polypeptide, has 29 azamines, molecular weight of 3485.

The effect of increasing blood sugar, stimulating the liver to increase blood sugar when blood sugar is lowered due to increased glycogenolysis, increased lipolysis in adipose tissue to create energy.

Mechanism of action mediated by cyclic AMP.

The normal concentration is 50-100 pg/ml, secretion depends on blood glucose concentration when blood glucose drops below 70mg% will stimulate alpha cells to secrete glucagon and vice versa. High levels of amino acids such as alanine and arginine after a meal stimulate glucagon secretion to increase the conversion of amino acids into glucose. Vigorous exercise also causes an increase in glucagon secretion.

Somatostatin

Is a polypeptide molecule consisting of 14 amino acids, with a molecular weight of 1640.

Inhibitory effect on insulin and glucagon release.

Inhibits secretion of digestive juices, absorption of food in the stomach, small intestine.

The half-life of somatostatin is very short, only 3 minutes, the concentration of factors related to food digestion stimulates somatostatin secretion.

Pancreatic dysfunction

Weaknesses

Diabetes. Causes: heredity, nutrition, infection. Often decreased or lost insulin secretory function of pancreatic beta cells.

Obesity also plays an important role in the pathogenesis of diabetes, in this case, due to decreased insulin receptors in the cells.

The disease manifests as eating a lot, but still being thin, tired, because glucose cannot enter the cells, the body always lacks energy. Patients are prone to skin infections, tuberculosis. Clinically, patients with diabetes often come to the doctor because of the symptoms called syndrome 4 many: eating a lot, drinking a lot, urinating a lot and losing weight fast. Tests have increased blood sugar, ketone bodies in the blood, high urine sugar... The disease usually requires regular insulin treatment, if not well controlled by treatment, the patient may gradually fall into a coma.

Usually divided into 2 types:

Type I: (IDDM: Insulin-dependent diabetes mellitus), insulin deficiency, occurs in young people   

Type II: (NIDDM) due to a decrease in the number of insulin receptors, usually after the age of 40, obese people.

In addition, diabetes is also found in:

The decreased affinity of the receptor for insulin.

Excess of hormones that cause hyperglycaemia such as glucagon, corticosteroids, GH.

Advantages

Because insulin is secreted a lot, causes pancreatic tumours, autoimmune diseases...

Characterized by hypoglycaemia, hypoglycaemic episodes often present with a rapid pulse, sweating, and fatigue. When blood glucose levels fall below 2mmol/l (0.35g/l) it leads to brain dysfunction with coma and possibly death.

Treatment is simple with an injection or intravenous infusion of glucose.