Insulin resistance: why the hormone cannot reach the cells

Diabetes mellitus – a group of endocrinological diseases characterized by chronic hyperglycemia. Every year the number of people with this diagnosis is growing rapidly: if in 2002 there were about 120 million people in the world with diabetes, then in 2016 their number was 415 million.

The catastrophic spread of diabetes contributed to the formation of even a separate area of ​​endocrinology – diabetology. Learn more about insulin resistance – key mechanism for the development of type 2 diabetes mellitus – read on estet-portal.com in this article.

The role of insulin resistance in the pathogenesis of type 2 diabetes

It is common knowledge that type 2 diabetes is also called non-insulin dependent diabetes. Description «insulin-independent» not entirely true from the point of view that insulin preparations are now widely used in the treatment of the disease. At the same time, in type 2 diabetes, there is not an absolute, but a relative deficiency of insulin: pancreatic beta cells produce sufficient, and sometimes even excessive amounts of the hormone for many years. But insulin itself cannot realize its effects due to the insensitivity of cells to it – insulin resistance.

Insulin resistance – this is a violation of the perception of insulin signals by cells.

That is why insulin deficiency in type 2 diabetes is called relative: the hormone is produced enough, but it cannot fully realize its effects.

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Before insulin resistance: how insulin normally works

In order to understand the mechanisms behind the development of insulin resistance, it is necessary to know how the hormone affects normal cell receptors and how it implements its effects. When blood levels of glucose rise, for example due to a meal, insulin needs to ensure that the glycemic level normalizes and glucose enters the cells. Insulin receptors are located on the surface of every cell in the body. The binding of insulin to them leads to the transport of the structural part of the receptor associated with the hormone into the cell by endocytosis – receptor internalization and subsequent activation of – protein kinases. They, in turn, trigger the protein phosphorylation cascade.

This is how the cell receives a signal that it is necessary to transport glucose inside. It does not have the ability to independently penetrate inside by endocytosis. For this, glucose needs the presence of a so-called glucose transporter. This protein at rest (when there is no influence of insulin) is located inside the cell as part of vesicles. After insulin enters, glucose, together with the transporter, enters the cell. After insulin has completed its main action, its molecule is destroyed in the lysosome, and the structural part of the receptor connected to it returns to the surface. This happens in healthy people.

Mechanisms of development of insulin resistance in type 2 diabetes

In type 2 diabetes mellitus, the above mechanisms for normalizing blood glucose levels are not fully realized. The formation of insulin resistance occurs due to the action of such mechanisms:

1. Receptor internalization insulin – endocytosis of the structural part of the receptor bound to insulin normally ends with the destruction of the ligand and the return of a part of the receptor to the surface. In type 2 diabetes mellitus, not only the ligand is destroyed, but the entire structural part of the receptor.
Decrease in the number of insulin receptors
2. on the cell surface;
Insulin
3. receptors are less sensitive: new receptors are formed by reading the genetic information about the necessary structure of proteins. The more often the process of gene transcription occurs, the less often the repair process occurs and the higher the probability of mutations. "New" insulin receptors over time become less and less sensitive to the influence of the hormone.

Abuse of food high in light carbohydrates and fats of animal origin is a factor in the development of type 2 diabetes.

It is worth noting that not all people with

have diabetes. In the development of this pathological condition, an important role is played by hereditary predisposition, which is a key link in the implementation of mechanisms for the development of insulin resistance. Thank you for staying with estet-portal.com. Read other interesting articles on the site in the "Endocrinology" section. You may also be interested in:

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