There are all sorts of ideas out there about the mechanisms behind high blood sugar in type 2 diabetics. Those who haven’t really studied it much tend to believe that it is because our bodies do not take in the proper amount of glucose, peripheral glucose uptake as it is known, because we are not sensitive enough to insulin.
This has been shown to not be the case and in fact we tend to take in plenty of glucose, and if not we’d actually be in a ketogenic state, not from eating a ketogenic diet but simply from not getting the uptake. This is not the case with diabetics unless they are quite insulin deficient, but when we do see this we do see the ketosis, and this can be extreme enough that one may get ketoacidosis, which can be fatal.
Type 2 diabetics make plenty of insulin generally, way too much actually, and we know this because we’ve measured it, and prior to that it was just assumed that we were insulin deficient like type 1’s are. There is a small percentage of type 2’s that don’t produce enough insulin, around 5% of us, where one gets double diabetes so to speak, a combination of type 1 and 2, and the type 1 component is autoimmune. We call this LADA or type 1.5, and this is not from beta cell exhaustion, it’s from excess beta cell death from the autoimmunity, the same thing type 1’s get but to a lesser extent generally.
Anyway, it’s not that we don’t take in enough glucose, and one’s blood sugar levels will rise to the point where the blood sugar levels alone will assure uptake, and insulin isn’t even needed for this, in spite of the myths. It is needed to take in an excess of glucose, so you can lower blood sugar with insulin, and that’s what insulin does, not feed the cells as much as clear the blood of glucose more quickly, although the price that is paid here is that if you keep doing this, you will damage the cells and they will become glucose insensitive as a protective mechanism.
So we know that the real problem is that we have too much glucose in our blood, and this comes from not a lack of insulin, but an oversecretion of glucagon, from the alpha cells in the pancreas mostly. There are two major hormones that are secreted by the pancreas that regulate blood sugar, insulin, which puts it down, and glucagon, which puts it up, and when you have too much glucagon your blood sugar will go up too much.
So what causes glucagon to go up? Well we know that high insulin levels over time will cause this, and this isn’t just a theory, we’ve proven this in experiments, starting with the work of diabetes pioneer Dr. Roger Unger. Dr. Unger showed that our alpha cells get poisoned from too much ceramide from too much fat, lipotoxicity, which is caused by too much insulin, and they become deaf so to speak.
Dr. Unger believed that this caused the alpha cells to be insulin resistant, deaf to insulin, and we’d even see insulin and glucagon go up in concert after a meal, which has been thought of as a paradox, because insulin is thought to suppress glucagon.
So this is where the story for us starts, none of this so far as been groundbreaking, and all of this has been known for decades. I’ve been looking into this process a lot more lately, and in particular, the role that glucose detection plays in glucagon secretion, and it actually makes sense that insulin and glucagon would go up together.
What really got me thinking more about this is a video lecture that I had watched originally a while ago and decided to watch it again because it’s got some interesting data in it, and then I realized that the real problem isn’t insulin sensitivity, it’s glucose sensitivity.
This lecture is pretty technical by the way and isn’t really the sort of thing diabetics in general would be watching, but those particularly interested are invited to give it a watch.
It addresses the two main defects that we see, and the first thing it looks at is the effects of infused glucose on type 2 diabetics, and clearly shows that our insulin response is muted when we infuse glucose, put glucose directly into our blood in other words.
This is interesting given that our insulin levels tend to be much higher than non diabetics, something that the professor doesn’t seem to be aware of, but when we put this knowledge together with his research, then the reason why we suffer from hyperinsulinemia has to be from the gut, from eating and having the food itself, not the glucose in the blood, drive our insulin levels too high.
This may not seem all that interesting of a finding at first glance but it really is, this tells us that it’s incretin hormones that must be doing us in. There are two incretin hormones, GLP-1, which type 2 diabetics don’t produce enough of, and GIP, which we tend to produce in excess, and GIP, which induces both insulin secretion and glucagon secretion, and in type 2 diabetics, this is what is wrong with us, we secrete both in excess.
So this is a huge deal actually. The second part of the presentation has to do with glucagon and glucose, and this part really interested me, and I came to the realization that it’s not insulin that suppresses glucagon, it’s glucose, and this is the defect we have, our alpha cells are glucose insensitive.
Insulin, by itself, should actually increase, not decrease glucagon, because when our insulin levels are too high this at least normally represents a risk of hypoglycemia, and glucagon may even be needed to save our life here. If we give a type 1 diabetic too much insulin, it will not suppress glucagon, it will increase it, and we might think that this is because blood sugar is dropping, and that has a lot to do with it, but under the conditions of excess insulin, this is very likely perceived as a danger that requires a response, and the response would not be to reduce glucose secretion in the liver.
So this is actually proven by insulin driving up glucagon in type 2 diabetics, and Dr. Rorsman in this video has shown this to be a normal phenomenon in type 2’s, and this is something that Dr. Unger has shown as well, to happen in some cases, although we weren’t aware that it was so widespread.
In normal people, we don’t see this, and this is because glucagon is normally regulated primarily by glucose levels in the blood, which is the main defect in type 2 as it turns out. So glucose is supposed to suppress glucagon, all things being equal, and insulin would increase it if not for the counter regulatory effect of glucose suppressing it, but this counter regulatory effect isn’t present, and it goes up instead in the presence of a meal.
This is another very big deal, we’re so focused on insulin sensitivity, but that’s not the problem at all, we need to get our alpha cells to be more glucose sensitive, and Dr. Rorsman believes that the loss of sensitivity here is due to electrical imbalances caused by mitochondrial dysfunction, which we know to be induced by excesses of insulin.
So to put this all together, we have excess GIP secretion in the stomach producing excess insulin secretion from the beta cells, this excess insulin damages our mitochondria, and this results in our alpha cells secreting too much glucagon from both the excess GIP, which is known to do this, in addition to their being glucose insensitive from mitochondrial damage.
I think that the mitochondrial damage is actually at the heart of all this because even in the presence of excess GIP, if we were sensitive to glucose as we’re supposed to be, the glucose sensitivity would keep our glucagon levels in check.
It is probably only because this glucose sensing mechanism is broken that GIP is able to raise glucagon as much as it does with us.
So the only way to really look to fix this problem is to look to make our alpha cells more glucose sensitive, which involves such things as reducing our cellular toxicity, from high insulin levels in particular, and also to look to improve GLUT1 reception in the alpha cells, which allows glucose into these cells, as well as improve cellular permeability in general, and also to look to repair mitochondrial damage.
There are supplements that can really help with healing all this, MSM, Q-10, and PQQ for instance, as well as things that raise glutathione levels like NAC. MSM is super interesting because it not only improves cellular permeability, it also is a sulfur containing compound, which may modulate the sort of intracellular electrical activity that is required for normal function, as insulin secreting drugs do, sulfonylureas, although these drugs end up secreting too much insulin at well, which end up adding to the problem.
Things that reduce cellular oxidation, particularly ROS, can also help this, as well as things that increase cellular energy, ATP, and a defect in potassium ATP channels within the alpha cells is primarily responsible for all this excess glucagon and all that excess blood sugar in turn. This is where Q10 and PQQ come in, and this isn’t the sort of thing that you are going to fix overnight, it took a long time to get this messed up and it will take a good amount of time to get better from it.
This stuff won’t fix itself though and unless we do, we’re just going to get worse and worse flying blind, which is clearly the case overall presently.