Recap Of Insulin Signaling in Glucose Metabolism - Online Tutor, Practice Problems & Exam Prep

Insulin, a 51 amino acid peptide, binds to its receptor, a receptor Tyrosine Kinase (RTK), activating it through autophosphorylation. This process phosphorylates insulin receptor substrates (IRS), activating PI3K, which converts PIP2 to PIP3. PIP3 then activates PKB, leading to GLUT4 translocation to the plasma membrane for glucose uptake. Additionally, PKB inactivates GSK3, promoting glycogen synthesis by activating glycogen synthase. This cascade ultimately decreases blood glucose levels post-meal, highlighting the critical role of insulin signaling in glucose metabolism.

Recap Of Insulin Signaling in Glucose Metabolism

Alright. So here in this video, we're going to do a recap or a review of insulin signaling on glucose metabolism. And so we're not going to cover anything new in this video that we haven't already covered in our previous lesson videos. If you're feeling really good about insulin signaling on glucose metabolism, then feel free to skip this entire video if you'd like because, again, there's nothing new in this video that we haven't already covered. However, if you're struggling with this even just a little bit, then stick around because a review like this one could be really helpful. Everything that we talked about in our previous lesson videos regarding insulin signaling on glucose metabolism will be covered. And so, if we start over here in the top left, of course, the 51 amino acid residue peptide, insulin, is going to act as the hormone or the ligand in this situation. Insulin is going to bind to the insulin receptor, which we're showing down below right here. And the insulin receptor is a receptor tyrosine kinase or an RTK. It has two alpha subunits here that will bind the insulin receptor, and then it also has these two transmembrane beta subunits that contain the cytoplasmic tyrosine kinase domains. They will autophosphorylate each other on tyrosine residues, which is why we have the 'Ys' here, which is the one-letter amino acid code for tyrosines. We end up getting these phosphorylated tyrosine residues on the insulin receptor. That fully activates the insulin receptor so that it can actually target its substrates, which are the insulin receptor substrates or IRS-1, for example. When the insulin receptor targets IRS-1 as its substrate, it will actually phosphorylate IRS-1 on tyrosine residues. And here we have the phosphorylated version of IRS-1. That activates IRS-1 so that it can act as an adapter protein, which recall is just a protein that lacks enzymatic activity and instead bridges other proteins together to activate them. This other protein that we see over here, PI3K or phosphoinositide 3-kinase, has what's known as an SH2 domain, and the SH2 domain, recall, will bind specifically to phosphorylated tyrosine residues here on IRS-1. When the SH2 domain of PI3K binds to the phosphorylated tyrosine residues on IRS-1, that actually activates PI3K. PI3K is a kinase, so we know that it's going to phosphorylate its substrate. Its substrate is actually PIP2 over here, and when it phosphorylates PIP2, it converts it into PIP3, which has one additional phosphate group on it. Then PIP3 is still associated with the cytoplasmic side of this membrane, and so it can only laterally diffuse within the membrane. PIP3 is going to laterally diffuse and associate itself with protein kinase B or PKB, and it will also laterally diffuse and associate itself with PDK1 or phosphoinositide-dependent kinase 1. Both PKB and PDK1 are also kinases themselves. When PIP-dependent kinase 1 binds to PIP3, it actually activates PKB1. PDK1, a kinase, is going to phosphorylate its substrate, which is PKB as we see here, using ATP as the phosphorylation source. You can see now we have the phosphorylated PKB, which fully activates PKB. The fully activated PKB, remember, is a protein kinase, protein kinase B to be specific. PKB will also phosphorylate specific target proteins. PKB will phosphorylate specific target proteins that we did not talk about in our previous lesson videos, but those specific target proteins that it phosphorylates will lead to the vesicle fusion with the plasma membrane, and these vesicles contain the glucose transporter GLUT4. That allows GLUT4, glucose transporter, to be expressed in the plasma membrane. GLUT4 will transport glucose from the bloodstream and transport it down its concentration gradient so that glucose can come into the cell. Also, PKB will phosphorylate specific enzymes that affect glycogen synthesis. More specifically, PKB will actually phosphorylate and inactivate GSK, glycogen synthase kinase, and it will phosphorylate GSK so that it becomes inactive. The inactive GSK3 will no longer be able to phosphorylate and inactivate GS, which is glycogen synthase. When GSK or GSK cannot inactivate GS, that allows GS to be active, glycogen synthase, which is an enzyme that synthesizes glycogen. It will act on the glucose, specifically this glucose over here that was brought into the cell, and it will convert this glucose into glycogen, maintaining the glucose concentration inside the cell relatively low so that the glucose in our bloodstream, which is relatively high after eating a meal, is able to be transported down its concentration gradient from the bloodstream into the cell, ultimately decreasing blood glucose concentration, which is really the primary effect here of insulin signaling on glucose metabolism, that blood glucose concentration is ultimately decreased after eating a high glucose meal. This here concludes our recap of insulin signaling on glucose metabolism and we'll be able to get a little bit more practice as we move forward in our course. So I'll see you guys in our next video.

What kinase phosphorylates IRS-1 in the insulin signaling pathway?

• A. IRS-1 auto-phosphorylates itself.
• B. PI3 Kinase.
• C. PDK1.
• D. The insulin receptor.
• E. PKB.

IRS-1 is an essential adaptor protein in the insulin signaling pathway. If IRS-1 was overexpressed in muscle cells, what effect would you expect to see on glycogen synthesis?

• A. Protein kinase B would remain inactive, resulting in increased glycogen synthesis.
• B. Protein kinase B would be overstimulated, resulting in increased glycogen synthesis.
• C. Protein kinase B would remain inactive, resulting in decreased glycogen synthesis.
• D. Protein kinase B would be overstimulated, resulting in decreased glycogen synthesis.

Here’s what students ask on this topic:

What is the role of insulin in glucose metabolism?

Insulin, a 51 amino acid peptide hormone, plays a crucial role in glucose metabolism by facilitating the uptake of glucose into cells. When insulin binds to its receptor, a receptor Tyrosine Kinase (RTK), it triggers a signaling cascade that leads to the translocation of GLUT4 transporters to the plasma membrane. These transporters allow glucose to enter the cell from the bloodstream. Additionally, insulin signaling activates glycogen synthase by inactivating glycogen synthase kinase (GSK3), promoting glycogen synthesis from glucose. This process helps lower blood glucose levels, especially after a meal, maintaining glucose homeostasis.

How does the insulin receptor get activated?

The insulin receptor, a receptor Tyrosine Kinase (RTK), gets activated when insulin binds to its extracellular alpha subunits. This binding induces autophosphorylation of the intracellular beta subunits on specific tyrosine residues. The phosphorylated tyrosine residues serve as docking sites for insulin receptor substrates (IRS), which further propagate the signaling cascade. This activation is crucial for the downstream effects of insulin, including glucose uptake and glycogen synthesis.

What is the function of GLUT4 in insulin signaling?

GLUT4 is a glucose transporter that plays a vital role in insulin signaling. Upon activation of the insulin receptor and subsequent signaling cascade, GLUT4-containing vesicles translocate to the plasma membrane. Once at the membrane, GLUT4 facilitates the uptake of glucose from the bloodstream into the cell. This process is essential for reducing blood glucose levels, particularly after a meal, and for providing cells with the glucose needed for energy production and storage.

How does insulin signaling lead to glycogen synthesis?

Insulin signaling promotes glycogen synthesis by inactivating glycogen synthase kinase 3 (GSK3). When insulin binds to its receptor, it activates a signaling cascade that leads to the activation of protein kinase B (PKB). PKB phosphorylates and inactivates GSK3, preventing it from phosphorylating and inactivating glycogen synthase (GS). Active GS then catalyzes the conversion of glucose to glycogen, facilitating glucose storage and helping to lower blood glucose levels.

What is the role of PI3K in insulin signaling?

Phosphoinositide 3-kinase (PI3K) plays a critical role in insulin signaling by converting PIP2 to PIP3. When insulin binds to its receptor, it activates insulin receptor substrates (IRS), which in turn activate PI3K. PI3K phosphorylates PIP2 to produce PIP3, a lipid second messenger that recruits and activates protein kinase B (PKB) and PDK1. This activation leads to downstream effects such as GLUT4 translocation to the plasma membrane and glycogen synthesis, ultimately reducing blood glucose levels.