insulin receptor sensitivity

[amestramgram]

hi
I was told in class that when a couple of insulin receptors bind insulin, the remaining unbound receptors decrease their sensitivity to insulin

has anyone else been told the same thing? if so, can you explain the chemical mechanism to me?

thanks !

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[Sol Rosenberg]

hi
I was told in class that when a couple of insulin receptors bind insulin, the remaining unbound receptors decrease their sensitivity to insulin

has anyone else been told the same thing? if so, can you explain the chemical mechanism to me?

thanks !

Which "insulin receptor" are you talking about? GLUT4? Na+/K+ ATPase?

 

[turkeyjerky]

Which "insulin receptor" are you talking about? GLUT4? Na+/K+ ATPase?

I assume that he or she is talking about the receptor tyrosine kinase that we all learn about in biochem.

I wasn't aware that insulin binds Glut4 or the sodium-potassium pump directly.

 

[amestramgram]

yes the tyrosine kinase

 

[Sol Rosenberg]

I assume that he or she is talking about the receptor tyrosine kinase that we all learn about in biochem.

I wasn't aware that insulin binds Glut4 or the sodium-potassium pump directly.

Man, it hasn't been that long since I saw that stuff, and it's fading already.....

 

[strv04]

I believe when insulin binds to its receptor the receptor/insulin complex is endocytosed or some jazz. Either way the more insulin you have floating around the less sensitive the cells are. Hence fat people who eat a lot have lots of insulin being released. This causes decreased senesitivity by the cells which can lead to type II DM. I'm sure the actually mechinism is much more complicated but that is my general understanding retained from endocrine.

 

[BigRedBeta]

I'm an M4 so I honestly don't know the answer (who knows if I ever did), but I'd guess that binding of insulin by the receptors causes some sort of conformational change in the insulin peptide, leading to the unbound receptors having a decreased affinity.

 

[Dr McSexy]

From what I've read recently due to my Endocrinology class, there a few reasons why more insulin desensitizes other unbound insulin receptors.

1.) As someone previously mentioned, insulin induces endocytosis and degradative pathways of its receptor .

2.) Insulin activates a number of serine/threonine protein kinases that eventually inactivate the insulin receptor substrate, thus terminating the pathway.

3.) Some people believe that insulin activates a "suppressor of cytokine signaling" pathway that leads to inactivation of several insulin receptor and insulin receptor substrate proteins.

 

[StIGMA]

The main ways a receptor could decrease its sensitivity to a molecule is if it were to gain or remove chemical groups (ie: phosphate) or if there were other factors (ie: proteins) binding it. Each would result in a conformational change that would affect its sensitivity. If unbound receptors are being downregulated, it seems an appropriate hypothesis that a feedback system is in place to keep the insulin-bound receptors unaffected by the downregulation. With insulin, I am pretty sure one method of downregulation is endocytosis, which is a common way to downregulate receptors.