Stukje van mij over insuline wat ik op 'n ander board heb geplaatst, voor de geinteresseerden (was 'n Engelstalig board, dus bear with it).
Insulin actions on cells and on flow of fuels.
Been reading a lot lately, and also concerning insulin. This piece I'm posting here is mainly based on the information available in the book 'Physiology' by Robert M. Berne. Hope this helps some people with a better understanding of the actions of insulin on cells and flow of fuels.
Insulin action on cells after binding to the insulin receptor.
As soon as insulin binds to it's receptor on a target cell (for example; adipocytes), a series of actions is started. After binding the hormone-receptor complex is subsequently internalized by endocytosis; the hormone is degraded. Dependant on the target cell, the receptor is either degraded (for example; lymphocytes), redistributed (for example; livercells), or recycled back to the plasma membrane (for example; adipocyte). Insulin downregulates it's own receptor, by increasing its rate of degradation and suppresing it synthesis.
After the binding mulptiple events occur at cellular level.
1. Initital signal transduction via the receptor tyrosine kinase activity. This kinase activity leads to ATP as substrate.
2. The now fully active tyrosine kinase phosphorylates tyrosines on two insulin receptor substrates (IRS-1 and IRS-2). These IRSs serve as a docking site and activating site for other protein kinases, protein phosphatases and more.
3. This IRS phosphorylation triggers a series of events which (de)activate numerous enzymes and translocate glucose transport proteins to the plasma membrane and more.
4. Binding of GTP to ras (protein involved in celullar signaling) in the plasma membrane. Ras activation stimulates cell growth and differentiation and activation of glycogen synthase and more.
5. In some target cells, insulin lower Cyclic Adenosine Monophosphate (cAMP, an important 'second messenger' in intracellular processes) levels.
This all happens very rapidly and within 1 minute, glucose transport into muscle and adipocytes is increased up to twentyfold by activation of the glucose carrier system in the plasma membrane. Especially Glut-4 is important, as it is specifically expressed in muscle and adipose tissue.
Insulin actions on flow of fuels
The main targets for insulin are the liver, the adipose tissue and the muscle mass. Insulin stimulates glucose and amino acid uptake from the liver to the muscle and inhibits amino acids leaving the muscle. Keep in mind it also stimulates glucose and free fatty acids uptake by adipose tissue (and inhibits free fatty acids leaving adipose tissue). Although it also inhibits glucose leaving the liver.
In the liver, extracellular glucose levels quilibrate rapidly with intracellular levels by means of GLUT2. Keep in mind GLUT2 isn't insulin sensitive. But insulin enhances inward movement of glucose by inducing hepatic glucokinase, which eventually leads to stroage of glucose as glycogen. Insulin also stimulates glycolysis and inhibits hepatic glycogenolysis (the proces of breakdown from glycogen to glucose). In addition, insulin inhibits gluconeogenesis (generation of glucose).
In muscle insulin stimulates the transport of glucose into muscle cells. Depending on the insulin concentration, 20% to 50% of the glucose that enters undergoes oxidation. The remainder is stored as glycogen in the muscle, caused by the glycogen synthase. The slow twitch fibers (oxidative, mainly used by long endurance sports) are more sensitive to insulin action on glucose uptake than are the fast twitch fibers (glycolytic, used by short high intensity actions, such as bodybuilders do). Furthermore, within muscle, insulin suppresses lipase (enzym for fat breakdown to fatty acids and glycerol) in inverse proportion to its stimulation of glucose uptake. This means free fatty acids (FFA) uptake in muscle is inhibited by insulin (together with oxidation). Meaning this especially effects the fast twitch fibers, which rely on FFA and oxidation for their energy.
Enhancement of protein metabolism by insulin.
Insulin enhances protein and amino acid sequestration in all target tissues, this makes it an anabolic hormone. In muscle, insulin stimulates the sodium depedent transport of amino acids across the cell membrane. The mechanisms include increases in gene transcription for numerous proteins, in rates of mRNA translation, ingeneral RNA syntehsis and in ribosome synthesis. Insulin decreases RNA degradation. It also inhibits proteolysis, which means it inhibits to protein breakdown. Leading to a reduction of release of BCAA's and aromatic amino acids from the muscle.
Insuline also indirectly stimulates the transcription of IGF-1 and suppresses the gene for one of the IGF-1 binding proteins, meaning there is more IGF-1, which is even more anabolic. IGF-1 is mainly produced in the liver, and after binding to it's receptor (IGF-1R), it highly promotes anabolic effects, such as increased muscle mass. Meaning insulin also indirectly promotes anabolic activity, by stimulation of the transcription of IGF-1.
Nee jongen, dan weet je écht nog niet wat een hongerklop is.
Wat ik wil zeggen: je lichaam gebruikt niet éérst al je glycogeen en schakelt daarna over naar vetverbranding. Hoe verklaar je anders dat ik na 3 uur trainen nog een anaerobe inspanning kan doen?
Zou nog maar eens in je boeken duiken als ik jou was.