Glut 2 of Hepatocytes/Pancreatic cells

[betterfuture]

I am trying to grasp the reason behind why Glut 2 has a low affinity for glucose concentrations. Is it because the Glut-2 are located in the liver and pancreas, which primarily function to just store the glucose instead of use it. Also, do these Glut-2 have high Km values because they allow insulin to release first before actually starting to uptake Glucose for storage purposes. If I can just get a little explanation for the function of the Glut-2 it would be quite helpful. Thank you.

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[aldol16]

This has to do with integrative metabolism. So the liver is basically the atruistic organ of the body. When blood sugar is low, the liver doesn't want to compete with your muscles or brain for the limited blood glucose so it doesn't use much. That's why the Km is high for GLUT2. Conversely, when blood glucose is high, the liver can use the glucose and it will take it up and store it as glycogen. So basically, glucose transport into the liver occurs mainly under high glucose conditions.

 

[centyrone]

My nutrition professor explained the high Km of Glut-2 in the following way. The pancreas and specifically the beta islet cells that will release insulin need to be able to respond to a broad range of blood glucose amounts. The high Km allows for this. If the Km was low such as it is with Glut-4, the Glut-2 receptors would be active almost constantly, even at resting blood glucose levels. This would mean that these beta islet cells would be constantly producing insulin, which at resting blood glucose levels is not desired. By have a high Km, there is the ability to have a wide range of response to a wide range of blood glucose levels. If blood glucose is barely raised above normal the cells will barely release much insulin, but as blood glucose levels rise, so too can insulin release. This is also true for the liver which needs to have a varying response to a broad range of glucose levels not just to resting glucose levels. Does this make sense?

 

[Astra]

I am trying to grasp the reason behind why Glut 2 has a low affinity for glucose concentrations. Is it because the Glut-2 are located in the liver and pancreas, which primarily function to just store the glucose instead of use it. Also, do these Glut-2 have high Km values because they allow insulin to release first before actually starting to uptake Glucose for storage purposes. If I can just get a little explanation for the function of the Glut-2 it would be quite helpful. Thank you.

Glut 2 receptors are found in in hepatocytes and pancreatic cells. They have a higher Km compared to Glut 4 receptors which are found in adipose and muscle tissues.

A higher Km because this will make the cells uptake glucose later on compared to muscle and adipose tissuses where glucose is used.

Excess glucose will then be transported into the pancreas and hepatocytes.

The importance of this is that fact that these cells is that these cells trigger insulin release. If you had a low Km value for these cells, then you would become hypoglycemic

 

[betterfuture]

My nutrition professor explained the high Km of Glut-2 in the following way. The pancreas and specifically the beta islet cells that will release insulin need to be able to respond to a broad range of blood glucose amounts. The high Km allows for this. If the Km was low such as it is with Glut-4, the Glut-2 receptors would be active almost constantly, even at resting blood glucose levels. This would mean that these beta islet cells would be constantly producing insulin, which at resting blood glucose levels is not desired. By have a high Km, there is the ability to have a wide range of response to a wide range of blood glucose levels. If blood glucose is barely raised above normal the cells will barely release much insulin, but as blood glucose levels rise, so too can insulin release. This is also true for the liver which needs to have a varying response to a broad range of glucose levels not just to resting glucose levels. Does this make sense?

So does Glut-2 serve to initiate insulin release before it itself uptakes glucose?

 

[centyrone]

So does Glut-2 serve to initiate insulin release before it itself uptakes glucose?

If I understand your question correctly then no. Glut-2 is the receptor on the membrane of the beta islet cells. Glucose is taken in from the blood by the beta islet cells and insulin release is triggered, proportionate in a way (because of the high km) to the amount of glucose that the cell intakes

 

[betterfuture]

Ok. I don't want to sound stupid, but I just want to clarify things so I can understand them first. So this is what I understood so far from your explanations.

So from what I interpreted from what you said is that first, Glut 2 takes in glucose when it reaches its Km value of ~15mM, like primarily after a meal. After glucose is uptaken into the pancreatic and liver cells, THEN insulin is released? Or does insulin release AT THE SAME TIME while GLUT 2 uptakes glucose?

I would have thought a little different. I thought that GLUT 2 acts as a glucose sensor, causing the release of insulin. And then, if there was an excess glucose, the GLUT 2 would then uptake glucose for storage. Is this correct?

 

[centyrone]

Ok. I don't want to sound stupid, but I just want to clarify things so I can understand them first. So this is what I understood so far from your explanations.

So from what I interpreted from what you said is that first, Glut 2 takes in glucose when it reaches its Km value of ~15mM, like primarily after a meal. After glucose is uptaken into the pancreatic and liver cells, THEN insulin is released? Or does insulin release AT THE SAME TIME while GLUT 2 uptakes glucose?

I would have thought a little different. I thought that GLUT 2 acts as a glucose sensor, causing the release of insulin. And then, if there was an excess glucose, the GLUT 2 would then uptake glucose for storage. Is this correct?

You're on the right track here. GLUT 2 is just a transporter for glucose. The Km value is just telling you the glucose levels required to take up 50% or half of all the GLUT 2 transporters. So at its Km value of ~15 half of the GLUT 2 transporters in the cell will be transporting glucose into the pancreas islet cells and the liver. At glucose levels lower than Km glucose will still be transported into these cells by GLUT 2 but only a smaller percentage of the GLUT 2 will be used. Above Km will be the same thing, more GLUT 2 transporters will be transporting glucose into these cells. Km just serves as the 50% mark. Now as glucose is transported into the pancreatic beta islet cells a biochemical reaction occurs that causes insulin to be released. So if more glucose is transported into the islet cells (by GLUT 2) then more insulin will be released.

 

[betterfuture]

You're on the right track here. GLUT 2 is just a transporter for glucose. The Km value is just telling you the glucose levels required to take up 50% or half of all the GLUT 2 transporters. So at its Km value of ~15 half of the GLUT 2 transporters in the cell will be transporting glucose into the pancreas islet cells and the liver. At glucose levels lower than Km glucose will still be transported into these cells by GLUT 2 but only a smaller percentage of the GLUT 2 will be used. Above Km will be the same thing, more GLUT 2 transporters will be transporting glucose into these cells. Km just serves as the 50% mark. Now as glucose is transported into the pancreatic beta islet cells a biochemical reaction occurs that causes insulin to be released. So if more glucose is transported into the islet cells (by GLUT 2) then more insulin will be released.

Thanks! You cleared it up quite well. And thanks to everyone else who helped.