This video explains the molecular mechanism of insulin .It also explains how the signal transduction cascade is affected during type I and type II diabetes
Hello in this video i’m going to talk about insulin mechanism of action so as you can see here after taking a lunch full of carbohydrate our blood glucose level our blood glucose level will increase so when we take food the food goes into the intestine and inside the intestine it would be converted into the smaller forms so look starch it would be broken down into
Glucose and glucose we’ll have to get inside the bloodstream and it will be spread around the body so what will happen in the cell of intestinal lumen there are sodium dependent glucose transporters also known as is g l t so it will take sodium ion inside as well as glucose so glucose will enter to the apical surface with the help of sg lt into the luminal cells
And there we have glute the glucose transporters so glucose transporter will take in glucose and glucose will enter into the bloodstream that means here represented as a capillary here glucose will enter into the clubhead capillary and would be spread around the body so what we now have the blood glucose level is pretty high say for instance now this glucose keeps
Circulating and get into the skeletal muscle so now what will happen into the happen to the glucose we will see so here is a cell so this is a skeletal muscle cell at the mean time when blood glucose level increases body also sends that blood glucose is pretty high so body will secrete insulin from the pancreas and this insulin will come here and bind to the insulin
Receptor on the surface of the skeletal muscle cell so the insulin to the receptor tyrosine kinase or also pronounced as rt k now the insulin will do stops inside the cell so that a preformed vesicles which contain route 4 that means the glucose transporter can dock in so insulin by binding ultimately triggers good for physical docking to the membrane site so once
The glue truth of it more loose fur vest physicalism docked to the membrane more the number of the glute 4 vesicles get onto the surface of the cell membrane now we will see insulin when binds to the rtk it will triggers a conformational change and that will lead to the tyrosine kinase activity of its cytosolic domain and the tyrosine residues are phosphorylated
Here you can see the tyrosine residues get phosphorylated and with this tyrosine residue another kinase can bind this kindness is known as pi3 kinase or pi3k so phosphatidyl inositol 3 kinase either it could directly drop to the phosphotyrosine residue or it can dock via the insulin receptor substrate or irs so once pi3 kinase bind and activate it pi3 kinase would
Convert it to 2 pip3 actually pi3 kinase phosphorylated spit – to tip 3 and this bit 3 which is phosphatidyl inositol 3 4 5 triss phosphate activates a kt or also known as protein kinase b actually it was found in act 8 retrovirus and hence the name so this act or pk b will go to the vesicles and it can convert rab gdp to gtp rab in gtp-bound form is active and
What happened in the normal state the adaptor proteins of this seagull are inhibited by a cap protein so what happens this pkb actually phosphorylates this cap and now the caps falls off when the caps fall off these vesicles could be loaded onto the kinase ii motors the skynet enomoto motors are trucks they will carry the vesicle to their desired destination here
In the membrane so these vesicles loaded onto a kinase team will move on the microtubules so the microtubules are the highways and ultimately the glute 4 vesicles will fuse into the membrane and allowing more and more glucose optic by this muscle cell and the muscle cell can utilize these glucose for energy purpose you remember the glycolysis and this signaling
Is pretty important to understand diabetes so in type 1 diabetes insulin level is pretty low so when insulin level is low this signaling doesn’t take pay that doesn’t take place and if take place it’s pretty inefficient so what happens we don’t have much this good for basic route 4 transporters on the membrane however in the type 2 diabetes insulin is okay insulin
Is formed but the receptor and the insulin interaction is not sensitive so insulin can bind to the receptor but doesn’t trigger the cascade of reactions or what happened in the type 2 diabetes any of these steps of this total signal transduction cascade could be faulty as a result this glute 4 vesicles would not fuse to the membrane and it will not allow glucose to
Enter the cell so another interesting aspect is is good for transporters blut for an exclusively found in skeletal muscle whereas glute 1 is found in rbc good tree in brain glue true in liver for instance in liver when glucose needed to be part it into glycogen soul evil will uptick with glue to transporter not to buy glute 4 and in brain so brain food is actually
Blucas so brain exclusively utilize glucose for energy so blend brain need to take up glucose by the tree if much of these transporter are not in the membrane so what will happen even if glucose is present in the peripheral region the semi cannot uptake glucose and cannot utilize so that happens into the diabetes where glucose is present into the peripheral area
Of the cells but the cells cannot utilize glucose as a result the blood glucose level is pretty high and that would lead to some pathological conditions hope you enjoyed the video thank you
Transcribed from video
Insulin : mechanism of action and diabetes By Animated biology With arpan