The main finding is that the oxidation of glucose can blocked, even in the presence of large amounts of injected insulin, by a modest quantity of a particular small molecule. This form of insulin resistance, if you want to call it that, does not seem to occur at the cell surface, so it's probably not mediated through the failure of insulin to mobilise GLUT4s. And, as glucose seems to enter the cells and disappear, the presumption has to be that it is "non oxidatively disposed" as the modern parlance has it. Probably to glycogen, there's not really anywhere else for it to go.
So what is this evil chemical which blocks glucose oxidation even in the face of hyperinsulinaemia?
Beta hydroxy butyrate. That's it. Ketone bodies (acetoacetate seems to work as well) are triggers for insulin resistance. Hence the appalling problems of type two diabetics on the Atkins induction diet. What problems? Oh, normoglycaemia and weight loss! Well, maybe there are problems long term or or or...
Again ketone bodies, one of the hall marks of carbohydrate or total calorie restriction, channel glucose away from muscles, toward brain and add a modest supplementary energy supply to brain tissue too.
It's exactly what you expect on an adaptive basis, exactly the same function as palmitic acid performs and clearly the two metabolic pathways are closely linked, though ketones seem to work downstream of the action of palmitic acid.
The fact that ketones do still allow insulin to move plasma glucose in to cells, and probably store it as glycogen, might be of interest to those who's blood glucose seems to do strange things after they eat medium chain triglycerides. MCTs (in rats anyway) undoubtedly spike both insulin and ketones, but usually result in normoglycaemia (insulin resistance?). But this is in a carbohydrate fed, glycogen replete rat. If you are initially glycogen depleted the shift to replete glycogen under ketones from MCTs might just leave you hypoing. No one has looked at this as far as I'm aware but ItsTheWoos' experience is interesting on this front...
Actually, looking carefully at the graph from Yeh and Zee, glucose does dip through an amount which might be clinically noticeable...
Anyway, there you have it. Metabolic poison number three, beta hydroxy butyrate. Evolution sure made a lot of b@lls-ups on the way to where we are today. I'm doomed, as always.
Peter
