Hey folks, Elliott here today. I'd like to go over another fundamental, but often counterintuitive idea in metabolic physiology and so I've titled this relaxation requires energy. The main model or the main the, an easy heuristic to. Understand what I'm talking about is to consider dead bodies, essentially dead bodies are ... their muscles within the few first few hours and days of mortality, they all contract.
And so here's a lecture at the university of Wyoming, basically talking about this phenomenon ATP is consumed at high rate by contracting muscles. The need for ATP in muscle cells is illustrated by the phenomenon of rigor mortis, which is the muscle cell rigidity that occurs in dead bodies for a short time after death.
In these muscles ATP has all been converted to ADP and the mitochondria cannot convert ADP back to ATP because there is no oxygen available. In the absence of ATP calcium transport proteins, stop pumping calcium into the sarcoplasmic reticulum and the calcium and the sarcoplasmic curiculum gradually leaks out causing the myin binding sites to be exposed on the Acton filaments of the MyFi,
the myocin proteins, grab the actin and pull once, but cannot release and pull again. The muscles therefore remain rigid in the position of death until the binding of myin or to Acton begins to break down. When you think about having a muscle cramp in your skeletal muscle, you can use the model of these dead bodies that essentially don't have enough energy.
And the reason they don't have enough energy is because It takes oxygen and glucose to turn ADP to ATP and so without both the oxygen and the glucose they can't relax.
So this is Harvard.
I don't know, health blog, if you will. And what do they say causes cramps: exercising without properly warming up. Okay basically a lack of blood flow. So similarly, a lack of oxygen and a lack of energy molecules, which could be for muscles that can be either fatty acids, I think pytuvate or glucose.
And then a lack of the appropriate electrolytes, so magnesium or potassium and an excess of lactic acid. Reduced blood flow to the muscles can also co cause cramps and essentially that's consistent with rigor, mortis. I just wanna make this point clear.
Let's take a quick look at
Open textbook from, British Columbia, Canada. And here's what they say is required for relaxation of skeletal muscle right here. The muscle fiber will repolarize which in some sense I is gonna be, what I would say is protein extension based on. Closing the gates in the sarcoplasmic reticulum, where the calcium was being released, essentially not allowing further calcium to be released while using then energy to drive calcium back into the sarcoplasmic reticulum.
This is the same story as rigor but just at a smaller scale, it takes energy to put the calcium in an organized manner in the sarcoplasmic reticulum here, they're just talking about what causes even fatigue the opposite of that is the use. They say it's requiring stores of ATP.
So those ATP stores get reduced during muscle function
lactic acid and the extra cellular environment in pH also affects the enzyme and protein activities of the cells and then electrolyte imbalances, are an issue and then finally, they're talking about the requirement for oxygen. Oxygen is required to restore ATP and creatine phosphate levels. And then it's also required to convert lactic acid to peruvic acid which would be and then also lactic acid into glucose, to reduce lactic acid, your cells have to use oxygen. The muscle cells have to use oxygen to rebuild their ATP. And I think I'm beating this horse to death.
Okay. So why is muscle relaxation so important?
So you have the endothelial cells. They're the ones that are the barrier between the the whole structure and the blood flow, the blood and then you have some glycocalyx around here and you have vascular smooth muscles around the AC the outside of that glycocalyx.
And so if you don't have enough systemic energy and you don't have enough ions, magnesium and potassium, these muscles won't relax, which means you're going to reduce the blood flow through your vascular system. And I think that's pretty key insight for how we work.
another type of cell I wanted to talk about was the nervous cell and I think we can basically think of the brain and nervous system acting very similar to what I just described. Although the actual contractions are not contractions per se. They're they're nerve impulses. So the energy demands of the brain are primarily met by glucose, which is oxidized through glyco.
And oxidative phosphorylation. So we prefer oxidative phosphorylation to produce ATP, it's just saying it has to the brain has to have energy available to respond rapidly this paper is trying to get at the impact of the inefficient production of ATP from glucose, which is outside the mitochondria in the cytosol basically it happens when there's not enough oxygen. And so they're talking about how a deficiency of oxygen would disregulate the nerve cells and create neurodegeneration. Okay. Yeah, so we're not gonna get into that paper, but just realize that nerve the nervous system and the nerve cells require a great deal of energy and that energy has to come from glucose.
All right here is a paper of a intervention. I would say that I'm I find fascinating. GIK so that stands for glucose, insulin, and potassium. And there, there are a number of papers on the uses of GIK and this is one just talking about it in. Cardiac surgery and all I really want us to take away from this is that an injection of glucose, insulin, and potassium
significantly reduced myocardial injury and improved hemodynamic performance in patients undergoing cardiac surgery. And then they have a nuance with folks that have diabetes. So counter to what all of the mainstream diet folks are saying, both insulin and glucose are favorable for VA.
I'm gonna say VA dilation. They don't say it in here. We'll get to that in a second. But essentially these are factors which get energy into the cell and allow what they're calling repolarization and potassium is probably the key to when and why insulin and glucose are both vilified because they're ignoring the fact that you need the right cofactors if you will, for efficient glucose uptake into cells. And this strange part of medicine, this niche of research, happens to know that glucose, insulin and potassium or they've provided evidence that's beneficial, at least in these cases, although they don't dig into the whole philosophy of it.
It also happens that. I was gonna say, maybe I'll have it real quickly in this, but the other paper that I've really paid attention to on, in relation to GIK is for the treatment of cancer. Researchers have essentially injected glucose, insulin, and potassium straight into can tumors, and it has essentially resolved the tumors
Okay. So potassium and VAD dilation. I wanted to point out that the literature calls that the effect of potassium on muscular cells, hyper polarization. We talked about polarization was basically activated by ATP. So energy creates polarization and then potassium, hyper polarizes.
Anyway it essentially. Causes vasodilation by let's go back to this
essentially, it relaxes these muscles around the edges of their vasculature through what they call hyperpolarization. I'm just gonna call that relaxation why they use that terminology. I don't really know.
And the vaso dilation. Results from again, re relaxation of a vascular smooth muscle cells subsequent to potassium stimulation by the ion. And they say it's from the sodium potassium pump. I'm not particularly a fan of the sodium potassium pump, but it doesn't really matter. It they're the models, various models work the same.
Okay. Here we go. Another paper on the role of potassium and regulating blood flow and blood pressure. So potassium is vasoactive and a direct infusion of potassium into an artery increases blood flow. And so this is basically just saying the same thing. A note for people trying to reduce blood pressure with potassium is that it takes a few weeks of increased potassium to get the full effect whereas sodium restriction can rapidly reduce blood pressure. But that's because most of the sodium is actually in the blood where in the potassium, it goes in the cells, sodium is typically kept in the blood fluid. And so when you restrict it, your kidneys will adjust with less water relatively rapidly. Okay. But I really wanted to focus on just the vaso dilation from potassium. They don't really talk about the requirement for glucose or insulin here, but let's keep that in mind. Potassium, glucose and insulin required for hyper polarization and vasodilation which is relaxation.
It happens to be the case that the pancreas requires potassium to secrete the right amount of insulin. So this is at a, at the systemic level to have insulin available, to put glucose into cells, you have to have sufficient potassium. the pancreas.
And so deficiency of potassium means you get a deficiency of insulin they basically won't secrete enough insulin, which means if you eat a bunch of sugar without potassium, then the sugar can't get into variety of cells
so that just goes to what the importance of potassium is in this whole consideration of energy and relaxation. Okay. So according to this paper insulin by itself has a, is also vasoactive has has it apparently stimulates insulin by itself, stimulates nitric oxide and.
Nitric oxide if I haven't made it clear already, but nitric oxide also induces vasodilation. So insulin by itself increases blood flow and that just doesn't seem to come up in any of the modern discussion of diet and insulin resistance. So increasing insulin through sufficiency of potassium, arguably is going to increase vasodilation, which is going to get oxygen to more peripheral tissues and also allow the vascular smooth muscles as we've just seen to relax, which kind of begs the question of whether we're dealing with
elevated glucose as the problem or insulin resistance?
Alright. Here's another paper talking about insulin mediated, vaso dilation and glucose uptake are functionally linked in humans. An infusion into an artery in the forearm causes vaso dilation, which the vasodilation seems to be augmented by simultaneous infusion of glucose. Then they speculate that the they're speculating that the the vasodilation may depend on insulin media, glucose updates. I think we've already covered this enough times, but essentially I don't.
I don't need to speculate. Let's see if we get into any greater discussion these data support the concept of a significant functional relationship between insulins metabolic and vascular actions possibly at an endothelial level. Yeah. Okay. No kidding. All right. that's from 1999. They just, I guess weren't with it until recently.
Okay. Insulin metabolic signaling increases, endothelial cell and nitric oxide production. We've already discussed that a little bit impaired vascular insulin sensitivity prevents that vascular relaxation. So basically if you're insulin insensitive, you are not gonna be able to relax your VA, relax your vasculature how to get insulin sensitive, how to reduce glucose in the blood is a topic for another discussion but needless to say, insulin working effectively is actively is a good thing in the body. So we don't want to necessarily blunt insulin.
Why all the confusion about insulin? Because it's not the only thing that allows glucose uptake in cells and the reason that we think it is now is because the pharmaceutical industry was selling insulin, overselling insulin basically in order to Monopolize the diabetes market.
So here we go, insulin is important and the regulation of blood sugar, but it's importance has been exaggerated because of the diabetes slash insulin industry. Insulin itself has been found to account for only 8% of the insulin, like activity of the blood with potassium being probably the largest. There probably isn't a process in the body that doesn't potentially affect blood sugar.
So I guess what he's really saying one is that potassium is way more important for getting glucose into cells than we would otherwise think and the reason that nobody talks about potassium and muscle relaxation and glucose uptake and insulin sensitivity is because it got whitewashed or scrubbed out of the textbooks essentially by the industry that sells insulin, cuz insulin is a highly profitable molecule. I'm not sure that's entirely true. I would say definitely potassium is highly. important in our consideration of insulin and insulin's action on cells.
I couldn't find a paper that said insulin requires potassium for cells to uptake carbohydrates, but that seems to be the case or predominantly the case when you have, when you eat a fruit Once you're potassium sufficient and you're producing a sufficient amount of insulin.
When you eat food, which has potassium in it, you need less insulin because the potassium helps the insulin pull the glucose into the cell. We, it may be that there's only a small amount of insulin required when there's a sufficient amount of potassium in the blood. And so the question would be what is the trade off between potassium and insulin for the for pulling glucose into cells and that's it. I just wanted everyone to realize ultimately that relaxation requires energy and we can think of using the corpse, a corpse as a model for a very unre, relaxed person. A very unen energized person and the vasculature is coated in muscles and and so if you're, if you're, if you've got muscle cramps and legs or in other places, guess what, you're probably not getting enough energy to them.
And also very likely that you're not getting enough energy to your vasculature system and your micro vasculature system. And your nervous system is equally under energized and that most likely is coming from any combination of potassium deficiency, insulin insensitivity and glucose dysregulation.
So that's all I've got. And thank you for listening.