Interesting stuff; I haven't read it yet but the discussion here seems to suggest that the problem with T2s is that they run out of fat cells and so have nowhere to store the spare BG.
I am struggling with this concept because as I understand it you don't generally create new fat cells but the ones you have grow larger. I may be wrong on this, though.
If it was just around fat cells, then if you lose for example a kilo of fat from your existing cells then you should normalise your BG until they fill up again. Unless the fat cells are insulin resistant and refuse to fill up quickly enough.
Edit: O.K. now I have read it and I can't quite track the logic.
It seems to suggest that "tissues" (I assume the liver and muscles and other organs) are crammed full of glucose and not insulin resistant.
O.K. that doesn't sound earth shattering; most T2s seem to have normal energy levels and also exhibit the normal "quick 4 lbs drop" when crash dieting which is attributed to the glucose stores (held in water) being depleted.
The article also says that the liver is turning glucose into fat (so listening to insulin) but still producing glucose (so not listening to insulin); this is where I start to lose the train of logic.
As I understand it, blood glucose is stored preferentially in the liver and muscles to provide an immediate energy source.
Once these tissues are full, then any remaining BG is converted to fat and stored in fat cells against future need.
This is encouraged by insulin, and while BG is elevated insulin is provided to encourage the cells to take up the spare glucose/glycogen.
Once the BG levels fall then insulin production drops and all is well.
However if BG levels aren't falling then the storage mechanism seems to be failing; Jason seems to be saying that the muscles and internal organs aren't insulin resistant so the logical culprit is the fat cells.
The liver is (possibly) trying to do all the right things but something isn't working in the rest of the system. Or there are two different metabolic pathways in the liver; one for converting glucose to fat for storage, and one for generating more glucose. Both these activities seem to be happening so perhaps one of these pathways is defective and not the other?
The article says
How in seven hells can this insulin resistant liver selectively be resistant to one effect of insulin yet accelerate the effect of the other? In the very same cell, in response to the very same levels of insulin, with the very same insulin receptor? That seems crazy. The same cell is insulin resistance and insulin super-sensitive at the same time!
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That seems to be the big question; the liver seems to be still generating more glucose when insulin should prevent this. The fact that it is producing glucose when it shouldn't be could be a key part of the equation. Although later on it is suggested that the liver isn't producing more glucose but there is just nowhere for the glucose to go so the assumption that the liver is producing more glucose is possibly incorrect..
All this seems to point to the fat cells.
If the fat cells take up glucose as mediated by insulin then become full, this suggests that either there are not enough fat cells or there is a problem within the cells converting glycogen to fat and so the problem is not in the insulin receptors (insulin resistance) but in the fat conversion process being too slow to clear the glucose already in the fat cells to make room for more glucose to enter the queue for conversion to fat.
Think of a bank with the front doors wide open but only one ageing and partially deaf bank clerk trying to process the ever growing queue until the queue spills out onto the pavement.
However we go round the loop again because as far as I can tell from trawling the Internet the process of converting glucose to fats within the fat cells is stimulated by insulin.
So perhaps what Jason is saying that it may be that the insulin receptors on the boundary of the cells may not be the issue - the "key and lock" analogy - but instead there is something not responding to insulin (or perhaps some trigger further into the cycle) or perhaps just not working fast enough within the fat cells to convert glucose to fat so the pancreas just keeps pushing harder and eventually gets tired and gives up.
This would tie in with the issue I mentioned further up; if you empty a fat cell then why doesn't it fill up again quickly and take the BG levels down.
Bottom line; there seems to be resistance built into the insulin cycle however it may be inside the cell itself instead of at the cell boundary. If you could transplant fat cells from a non-diabetic into a diabetic and monitor their performance this might give interesting results.
