Glut2/Glut4

[deleted783484]

- How come glut2 is said to be insulin independent if it senses the release of insulin to store glut2 in hepatocytes?

- I understand that glut4 has a Km similar to the concentration of glucose so it gets saturated fast but how come glucose influx can still occur if the glut4 receptors are saturated? And what's the relation with it being zero order?

Thanks!

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[Pono_0001]

I think insulin independent corresponds to the opening and closing of the channel. And ya if it's saturated glucose won't keep coming into muscle cells. why should it when that's more of a main job of the liver.

 

[yeasureyoubetcha]

- How come glut2 is said to be insulin independent if it senses the release of insulin to store glut2 in hepatocytes?

GLUT2 is a "sensor"...it doesnt sense insulin though.

GLUT2 is insulin independent (Liver and pancreas), GLUT4 is insulin dependent (on muscle, adipose, heart). GLUT2 has a higher Km and so transport is not maximally active at low concentrations. Postprandially when blood glucose is higher than the km transport into liver and pancreas will be high. GLUT2's involvment in insulin release is in the pancreas. High glucose in pancreatic beta cells will drive glycolysis and oxphos producing a high ATP/ADP ratio within the cell. The high ATP phosphorylate an ATP sensitive K channel closing it. This depolarizes the beta cell-->influx of Ca-->vesicles fuse with plasma membrane and release insulin.

GLUT2 is said to be independent because it does not require insulin to be present on the cell membane and take in glucose. Insulin literally tells the cells that it effects to preformed GLUT4 containing vesicles sitting below the PM to dock with it and suck in glucose.

- I understand that glut4 has a Km similar to the concentration of glucose so it gets saturated fast but how come glucose influx can still occur if the glut4 receptors are saturated? And what's the relation with it being zero order?

Glucose keeps coming into muscle cells and hepatocytes because hexokinase and glucokinase respectively phosphorylate glucose very quickly after they get in the cell converting it to something else to maintain the gradient into the cell.

 

[deleted783484]

GLUT2 is a "sensor"...it doesnt sense insulin though.

GLUT2 is insulin independent (Liver and pancreas), GLUT4 is insulin dependent (on muscle, adipose, heart). GLUT2 has a higher Km and so transport is not maximally active at low concentrations. Postprandially when blood glucose is higher than the km transport into liver and pancreas will be high. GLUT2's involvment in insulin release is in the pancreas. High glucose in pancreatic beta cells will drive glycolysis and oxphos producing a high ATP/ADP ratio within the cell. The high ATP phosphorylate an ATP sensitive K channel closing it. This depolarizes the beta cell-->influx of Ca-->vesicles fuse with plasma membrane and release insulin.

GLUT2 is said to be independent because it does not require insulin to be present on the cell membane and take in glucose. Insulin literally tells the cells that it effects to preformed GLUT4 containing vesicles sitting below the PM to dock with it and suck in glucose.


Glucose keeps coming into muscle cells and hepatocytes because hexokinase and glucokinase respectively phosphorylate glucose very quickly after they get in the cell converting it to something else to maintain the gradient into the cell.

First explanation makes perfect sense, thank you. However, for the second my question is how is the glucose able to enter if the transporter is blocked?

 

[yeasureyoubetcha]

First explanation makes perfect sense, thank you. However, for the second my question is how is the glucose able to enter if the transporter is blocked?

I'm unsure of which transporter you're referring to but GLUT4 is held in vesicles near the surface of the PM. Nothing is "blocked". Insulin merely causes the GLUT4 containing vesicles to fuse with the plasma membrane. It does other stuff in the cell too though. Were you talking about the K channel?

 

[deleted783484]

I'm unsure of which transporter you're referring to but GLUT4 is held in vesicles near the surface of the PM. Nothing is "blocked". Insulin merely causes the GLUT4 containing vesicles to fuse with the plasma membrane. It does other stuff in the cell too though. Were you talking about the K channel?

The Kaplan book states " the km of glut4 is close to the normal glucose levels in the blood this means that the transporter is saturated when blood glucose levels are just a bit higher than normal"

I guess i'm confused on what this means?

 

[yeasureyoubetcha]

The Kaplan book states " the km of glut4 is close to the normal glucose levels in the blood this means that the transporter is saturated when blood glucose levels are just a bit higher than normal"

I guess i'm confused on what this means?

Normal serum glucose: 4-8mM
GLUT2 Km: 15-25mM
GLUT4 Km: 5mM

So yes. Postprandially when glucose goes super high GLUT2 will be involved in lots of insulin release. Lots of GLUT4's will fuse with the membrane of heart, adipose, skeletal muscle and since [Substrate] >>>>Km -> Rate of transport = Vmax, GLUT4 gets saturated to bring down serum glucose