Originally Posted by WereBear
This suggests that it is the inflammatory effects of insulin which create the poor health outcomes?
I don't know if insulin causes inflammation, or if the disease process of atherosclerosis involves inflammation. I think it's possible that inflammation is not an a priori, but once it's there the disease accelerates, i.e. an infection for example.
Inflammation is not a disease in and of itself, but a response to disease, particularly acute conditions, i.e. injury. Atherosclerosis can be seen as an injury of the arterial wall, so inflammation would occur as a response to this injury. If the injury is chronic through hyperinsulinemia (or through some other chronic cause like a bacteria or something), then inflammation would also be chronic. So in that sense insulin causes injury to the arterial wall, but I don't know the specific mechanism.
In my understanding of the actions of insulin, I think the mechanism is deregulation of various cellular processes, most importantly fuel and enzymes, specifically with hyperinsulinemia, normal insulin level shouldn't cause disease since it regulates processes normally. Just like in liver cells, insulin shuts down ketogenesis in all cells, but I think I don't have to invoke this, since the lack of ketogenesis in the liver alone is enough to explain fuel deregulation in all cells that require ketones.
In the other extreme - diabetes type 1 where there's no insulin - there's no synthesis of various things essential to cellular functions like enzymes and protein for example, yet there's tons of fuel as glucose and ketones. And apparently, there's no atherosclerosis either. We could conclude that glucose itself is not the agent that causes the injury to the arterial wall, but merely the trigger. With a high-carb diet, there's lots of glucose coming in, so there's lots of insulin produced to handle that, and we now have a better overall picture of the sequence.
But it's not a complete picture. A high-carb diet is not the only cause, it's just the primary cause. This is in line with the idea that going low-carb can be used as a diagnostic tool to expose underlying conditions that also act the same way as a high-carb diet, i.e. causes hyperinsulinemia. So now we look at the PPAR-x pathways in the liver, where insulin-degrading enzyme does its thing to degrade insulin. When there's no IDE, insulin rises. However, this means BG should go down, but it doesn't, so when IDE is intefered with, there must some parallel effect on glycogenolysis or glucogenesis going on, maybe glucagon or other hormones that stimulates glucose release and/or production from the liver.
But again it's not a complete picture. I don't see how insulin causes injury, there must be something else going on. I bet on some pathogen. All bacteria - all pathogens - are opportunistic in nature, they will do what they do the instant the opportunity presents itself. Well, when cellular processes are disrupted all over the place, that's the opportunity. It's a bit like a supermarket that loses its doors so it remains open at night but doesn't have anybody working there at that time, so even people who are not bad just walk in and take whatever they want, rather than just the really bad people who would otherwise break in. See? Opportunistic pathogens will take over once there's hyperinsulinemia to deregulate standard cellular defenses.
We have all kinds of pathogens all the time, but they never bother us normally because we can handle them just fine when everything's working right. On the skin, tons of them, no problem. In the gut, tons of them, no problem. Tonsils, appendix, tons of them, no problem.
Pathogens are living things, they evolve and adapt. It's likely that some have adapted to at least maintain their preferred environent, once this environment has been established a priori, if they haven't developed a means to create this environment in the first place. In there somewhere, it's possible that those pathogens have the ability to deregulate the PPAR-x pathways and IDE so that insulin is not degraded, so that the cellular processes that normally handle those pathogens don't work properly.
Throughout all this, inflammation will invariably come into play (because we're talking injury), but not necessarily as an initial causal factor.
Don't take any of this too seriously, I just thought this up in a few minutes. Anyways, any of this make sense to you?