GLUT4 and insulin

[MudPhud20XX]

As far as I know, GLUT4 is insulin dependent. However, in Kaplan biochemistry it says as below:

"GLUT4 translocation to the cell membrane in skeletal muscle is stimulated by exercise. This effect, which is independent of insulin, involves a 5' AMP-activated kinase."

What am I missing here? Why does it say that the effect is independent of insulin?

Many thanks in advance.

---

Members don't see this ad.

 

[thinkbig]

U r not missing anything ... In exercise no need for insulin to get glut4 in to membane


Sent from my iPhone using Tapatalk 2

 

[Transposony]

GLUT4 translocation in both adipose tissue & skeletal muscle is induced by Insulin which is produced in response to high blood sugar levels.
However, when the blood sugar levels are normal and muscle needs more energy the GLUT4 translocation during exercise is induced by 5' AMP-activated kinase in response to increased AMP:ATP ratio which is independent of Insulin since there is not much Insulin release during normoglyciemia but exercizing muscle need glucose ASAP.

That's why exercise is so important in diabetics since when there is not enough Insulin around to take care of glucose the muscle will burn that excess glucose with the help of 5' AMP-activated kinase.

 

[notbobtrustme]

Think about it physiologically and biochemically. Does it make sense to release insulin when your body is already starved for glucose, as under exercise conditions? You would shunt glucose into bodily tissues that would not necessarily need it while tissues that do need extra energy might "starve" so to speak. So nature came up with a way to shunt glucose into metabolically active tissues without the need for insulin by relying on the same transporter.

 

[Juan Solo]

You are right ( and as are the people who have commented).
GLUT4 translocation to the plasma membrane is regulated in an insulin dependent manner and independent manner;
Insulin-dependent manner: Insulin binds to insulin receptors leading to activation of AKT ( and many other signaling/binding proteins) and this translocates a specific compartment/vacules of containing GLUT4 (or GSV compartments). This translocation happens rather quickly (minutes) from the onset of insulin signaling. Research is still ongoing to elicit the mechanisms involved after AKT.

Insulin-independent manner: In times of exercise or metabolic stress/starvation this will lead to activation of AMPK and then PKA. This also leads to promoting an increase in GLUT4 translocation to the plasma membrane. The source of the GLUT4 is still a debate ( GSVs, de novo or other sorting vacules, or promoting retention of the GLUT4 in the plasma membrane). Another difference is that this happens over a much longer time period and is not as acute acting or robust as the insulin pathway initially. However, this pathway is exploited in treating type-2 diabetes with Metformin and other drugs that activate AMPK and PKA pathways. Since type-2 diabetic patients usually have some form of insensitivity to the insulin-dependent pathway, this existance of this second insulin pathway becomes extremely advantageous.

Finally, tissues that have relevant levels of GLUT4; skeletal muscle, adipose and liver.
Hope this helped.
GL

 

[ulikedaggers]

I don't think there's GLUT4 in the liver. The liver mainly has GLUT2 (bidirectional, high Km, high Vmax) so it can regulate blood glucose levels. If the liver was insulin dependent (i.e. if it had GLUT4), it would compete with muscle/adipose and also not be able to release glucose in response to glucagon.

 

[Transposony]

I don't think there's GLUT4 in the liver. The liver mainly has GLUT2 (bidirectional, high Km, high Vmax) so it can regulate blood glucose levels. If the liver was insulin dependent (i.e. if it had GLUT4), it would compete with muscle/adipose and also not be able to release glucose in response to glucagon.

Well caught.....Thanks.

 

[BurberryDoc]

Adding to @notbobtrustme's comment, if you had insulin circulation in substantive levels during excercise, you would very quickly deplete blood glucose as it is uptaken into the active muscle tissue, and you would actually black out from low glucose delivery to the brain.