Our discussion of this video in the first 7 segments has actually dealt with Dr. Unger's view of type 1 diabetes, and although that's outside the scope of this site, being a site dealing with type 2, a lot of this material is important for us because it helps clear up some of the misconceptions we have about type 2 diabetes as well.
Most importantly, it elucidates very well the roles of both insulin and glucagon in maintaining glucose regulation and where they go wrong, and the mechanisms are the same regardless of what type of diabetes you have.
Now Dr. Unger moves on to looking at the disorder we're most interested in, type 2 diabetes, and he starts out by speaking of some of the myths, the dogma as he puts it, surrounding this disease.
He starts by listing the proposed causes of type 2, and mentions genetic defects, insulin resistance, beta cell exhaustion, glucotoxicity, low redox, and obesity. I'm not exactly sure what he means by low redox but it may be the idea that our cells lack the capacity to take in glucose and this is behind the high blood sugar we get.
Lipotoxicity is another major one, where we get too much fat in our cells basically, and this causes cellular malfunction, but that's part of the insulin resistance side. There are two sides to this idea though and one of them is the insulin resistance from the insulin itself, high levels of it in other words, and the other is from the cells resisting due to other causes, such as lipotoxicity.One he doesn't really mention and one that is pretty popular these days is related to obesity but doesn't require it, which is the notion that the increased amount of carbohydrates that we eat these days influences things, and that's a pretty popular notion, as is things like lack of exercise, environmental toxins, and a number of other things.
So the causes of type 2 diabetes are quite controversial, and this is just a partial list of things that are thought or have been shown to influence it, and it's at the very least much more complicated and much more controversial in origin than type 1, as Dr. Unger points out.
While Dr. Unger admits that all these things are factors in the development of type 2 diabetes to some degree, he proposes that the fundamental issue is lioptoxicity, and in fact he is the one who first put this idea forth years ago.
So he is saying though that this is what causes diabetes, specifically lipotoxicy of pancreatic islets, which can be reversed by reducing dietary induced hyperinsulinemia and lipogenesis. Hyperinsulinemia by the way is what is behind this excess lipogenesis, so this boils down to our insulin levels are too high and we need to reduce them to recover from this disease, and conversely, if we keep increasing them we'll get worse.
This was a very novel idea back when Dr. Unger proposed it many years ago, and while it has caught on a lot more since, it surely hasn't caught on near enough. I think that there may be more to do than just reduce the dietary induced high insulin levels though, but I do think that this is a big factor in diabetes for sure, and is the reason why dietary restriction tends to work so well with so many patients.
It's important to know why this works though, a lot of people who restrict glucose think that it's the fact that they are introducing less glucose into their system that is what is helping their blood sugar, but we know that's not it at all, and going back to the type 1 experiments, we could remove both their insulin and glucagon potential and they could eat what they want, because they wouldn't be diabetic anymore.
The lipotoxicity part is super important as well, and this actually gets even more complex than we'll be dealing with in this lecture, but we need to remember here that the goal is to reduce the toxic load of fat in the cell and that's the primary pathology here, and reducing insulin is just one influencer on this, albeit the most significant one.
This really all boils down to an even simpler concept I would say, and that's to eliminate excess free fatty acids in our bloodstream, and high insulin influences this a lot, through excess lipolysis, but is not the only thing, one's diet influences this a lot as well.
Dr. Unger now compares the slide of the type 1 diabetic, with only alpha cells in their pancreatic islets, to a type 2, and guess what, the type 1 has no beta cells, where the type 2 has an above average amount. So Dr. Unger then asks, with extra insulin capacity, why do we then have hyperglycemia as type 2's?
So he did a study with normal and obese rats. The normal rats had normal islet lipids and normal blood glucose. In the obese rats that developed diabetes, at the point where their blood sugar shot up, their islet lipid levels shot up as well, in concert. So he looked at the lipotoxic beta cells under a microscope and found that they were indeed severely damaged.
In humans, we have observed that in cases of impaired glucose tolerance, the levels of pancreatic fat are higher in obese subjects than in lean subjects, something to be expected, but when we look at subjects with impaired glucose tolerance, the percentage of pancreatic fat is more than twice as high.
Now we turn to the alpha cells, and Dr. Unger shares some measurements he made many years ago on the insulin sensitivity of alpha cells in diabetic and non diabetic subjects. In non diabetics, glucagon was suppressed 150 times more per unit of insulin in non diabetics. This is huge and in itself explains the phenomenon of diabetes, as even higher amounts of insulin aren't going to do a good job at all at suppressing glucagon as it should, and this is going to lead to a lot more glucagon being secreted, and that's exactly what we see with type 2 diabetes.
Next, he goes into the mechanisms of lipotoxicity a little more, which is where we will pick this up in Part 9.