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Hello, in this video we will talk about the mechanism of action of insulin. we will mainly focus on insulin receptors, intracellular signaling pathways where learning medical concepts is as easy as watching cartoons. as we already know, insulin is secreted from the β cells of the pancreas. through portal veins, this secreted insulin first goes to the liver. liver has an
Enzyme called insulin-degrading enzyme also known as insulinase. more than half of insulin is removed from the circulation. the insulin that escapes the liver is then available to act on other tissues. the main targets of insulin are liver, muscles and adipose tissue. based on this, you might now be able to predict the location of insulin receptors. it has 2 identical
Α chains that are entirely outside the cell. and 2 identical β chains that have extracellular, transmembrane intracellular domain of the β chain possesses tyrosine kinase activity. thus insulin receptors are an example of catalytic receptors. first the insulin binds to the α chains outside the cell. this binding increases the tyrosine kinase activity of the β chain
Inside the cell. these activated β chains now phosphorylate tyrosine residues on each other. now these phosphorylated tyrosine residues attract downstream molecules. important among them are insulin receptor substrate (irs) proteins. at specific tyrosine residues by the insulin receptor. to which various downstream signaling proteins bind and then become activated.
Irs-1 has multiple such binding sites so that a single irs molecule there are two major signaling pathways triggered by this machinery. let’s first talk about the phosphatidylinositol 3-kinase (pi3k) pathway. in this, first, pi3k binds to phosphorylated irs as we have already seen. to form phosphatidylinositol 3,4,5-trisphosphate or pip3. pip3 then recruits and activates
Phosphatidylinositol-dependent kinase or pdk. then pdk phosphorylates a protein called akt or pkb. and there are multiple pathways downstream to this. eventually they produce major changes in glucose and protein metabolism it causes the insertion of glut4 containing vesicles into the cell membrane. this leads to the increased entry of glucose into the cell. or irs
Activates a protein called growth factor receptor-bound protein 2 both phosphorylated shc and activated grb2 activate sos. then we have a series of events of the mapk pathway. we already discussed that pathway in the video on receptor tyrosine kinase. the result of that pathway is increased gene expression and growth. first, the overall effect of insulin signaling is
Increased anabolic activity and growth second, not all the pathways are expressed in all the tissues. for example, the insertion of glut4 on the cell membrane is seen only in skeletal muscles and adipose tissue, but not in the liver. third point is regarding time delay in the appearance of different events. effects like increased entry of glucose as well as increased
Entry of amino acids, changes in the activity of metabolic enzymes take a little longer, much slower effects include changing the rates of translation and transcription. so this was all about the mechanism of action of insulin. upon activation, first there will be cross phosphorylation of tyrosine residues. pi3k pathway that leads to changes in the metabolism of glucose
And proteins and mapk pathway that increases gene expression and growth. if you feel this video will help your friends and colleagues, and don’t forget to subscribe because lots more to come. at nonstop neuron, learning medical concepts is as easy as watching cartoons.