Viewing a single comment thread. View all comments

backroundagain t1_j15opxy wrote

Reply to comment by derpderp3200 in How and why do diet and lifestyle changes reverse insulin resistance? by derpderp3200

There's a chance you're conflating two different concepts. Peripheral insulin insensitivity is often a function of peripheral insulin receptor expression and/or cytosolic signal impedance. Exercise may improve this in a couple ways, including the "insulin like effect" of contracting skeletal muscle as mentioned above: https://www.ncbi.nlm.nih.gov/books/NBK537322/ to be clear though, this mechanism is not sufficient to completely replace pancreatic secretion, otherwise exercising type 1 diabetics wouldn't need to take insulin.

Pancreatic signaling for the release of insulin, the ability to release insulin via beta cells, and the production of viable insulin would be separate mechanisms with their own pathologies.

4

derpderp3200 OP t1_j15tw54 wrote

What is "cytosolic signal impedance"? This is the first time I have come across this term.

Oh, I understand, so the impairments in beta cell function are a secondary, later, consequence of insulin insensitivity, which typically is at first driven by... what exactly?

Aside from uptake by muscle, what else plays a role here?

1

Beginning_Cat_4972 t1_j190rgw wrote

Two things need to happen for insulin receptors (or really any receptors) to work. 1) The receptors need to be expressed. This is the actual production (transcription/translation)of the protein. There are a lot of steps between transcription and getting the insulin receptors to the cell membrane. Any of them could be disrupted and then there's always post translational modifications such as glycosylation that can muck things up. 2) Binding of the insulin receptor has result in an intracellular signal cascade, leading to glucose receptors being transported to the cell membrane. I think what is meant by cytosolic signal impedence is that something gets interrupted between insulin receptor binding to glucose receptor translocation. Or even cell signaling to initiate insulin receptor expression.

It's hard to accurately describe the process of insulin resistance as being linear or having a single inciting event. It's more of a breakdown of the entire, circular(ish) system. But I suppose I think of insulin resistance "starting" in the cells that have the most insulin receptors like fat cells.

1

derpderp3200 OP t1_j1ai4b8 wrote

Glucose receptors, or transporters?

How does cytosolic signal impedance develop, here?

1

backroundagain t1_j1abhpe wrote

What is "cytosolic signal impedance"? This is the first time I have come across this term.

The cellular mechanism of action of insulin can generally be grouped under a "second messenger system". This means that the signal its self (initiated by the insulin molecule) does not actually enter into the cell, but is transduced from the outside to a signal cascade on the inside (cytosolic side).

As such, a receptor system will have an extracellular component, a transmembrane component, and a cytosolic component. Cytosolic impedance (of the insulin signal) can occur as a function of the expression of a particular factor (protein) which interferes with the signal transduction on the cytosolic side of the receptor.

If you want to read the nitty gritty, here is a decent reference:

https://www.ncbi.nlm.nih.gov/books/NBK378978/

Oh, I understand, so the impairments in beta cell function are a secondary, later, consequence of insulin insensitivity, which typically is at first driven by... what exactly?

Beta cells are thought to be impaired by an autoimmune (or autoimmune like) attack on beta cells, though I think this is still up for debate. If they get taken out, you do not secret insulin, this is often a characteristic of a type 1 diabetic (vs. a type 2 in which you tend to see a decrease in the sensitivity down stream, in some cases as described above.)

1