Insulin activates target cell receptors and results
Insulin binds to the subunit of its receptor, causing autophosphorylation of the receptor - the subunit, which in turn induces tyrosine kinase activation.
To initiate its action on the target cell, insulin first binds to and activates the membrane receptor, which is a protein with a mass of about 300,000 kDa (figure). It activates the receptor causing the following effects.
Figure. Diagram of the insulin receptor. Insulin binds to the subunit of its receptor, causing autophosphorylation of the receptor - the subunit, which in turn induces tyrosine kinase activation.
Activation of the receptor tyrosine kinase initiates an intracellular phosphorylation chain that increases or decreases the activity of enzymes, including insulin receptors, that mediate effects on glucose, fat, and protein metabolism. For example, glucose transporters are delivered to the cell membrane to aid glucose entry into the cell.
The insulin receptor consists of four subunits, which are held together by disulfide bridges: two alpha subunits located completely outside the cell membrane and two beta subunits that cross the cell membrane, protruding into the cytoplasm. Insulin binds to the alpha subunit on the outside of the cell, but by binding to the beta subunit, parts of the beta subunit inside the cell become auto phosphorylated. Thus, the insulin receptor is an example of a receptor-binding enzyme, discussed in Chapter 75. Autophosphorylation of the beta subunit of the receptor activates the local enzyme tyrosine kinase, which induces phosphorylation. of many other intracellular enzymes, including a group called insulin-receptor substrates (IRS). Different types of IRS (eg, IRS-1, IRS-2, and IRS-3) are expressed in different tissues. In reality, they activate some enzymes while inactivating others. In this way, insulin directs the intracellular metabolic machinery to produce the desired effects in carbohydrate, fat, and protein metabolism. The following are the major final effects of insulin stimulation:
1. Within seconds of insulin binding to the membrane receptor, the cell membranes of about 80% of the body's cells markedly increase glucose uptake. This activity is especially true in muscle and fat cells, but it is not true for most neurons in the brain. Glucose is transported into the cell and is immediately phosphorylated and becomes the raw material for normal carbohydrate metabolism. The increased glucose transport is thought to result from the transfer of multiple intracellular vesicles to the cell membrane; The vesicles carry many glucose transport protein molecules, which attach to the cell membrane and facilitate the easy uptake of glucose into the cell. When insulin is no longer effective, the vesicles detach from the cell membrane in 3-5 minutes and return inside the cell for reuse as needed.
2. The cell membrane becomes more permeable to amino acids, K+, PO43-, due to increased transport of these units into the cell.
3. Slower effects appear within the next 10-15 minutes due to changes in the activity of intracellular metabolic enzymes. This effect is the main result of the change in the phosphorylation status of the enzymes.
4. Longer lasting effects continue to occur for hours, even days. It results from changes in the rate of mRNA translation at the ribosome to form new proteins and is still slow to work due to changes in the transcription rate of DNA in the nucleus. In this way, insulin compensates the intracellular enzyme machinery to exert some of its metabolic effects.