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Старый 29-01-2018, 07:21   #12
 
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Re: Дневник Nikolaivanych

Базовая физиология, о которой, кажется, не знает ни один "кето человек".

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Basic physiology that no keto person seems to be aware of. https://www.youtube.com/watch?v=IFlNlwWMfxM


Дальше текст ролика (на английском)
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Does losing all your money stress you out? If so you probably feel like your liver does when it's engaging in gluconeogenesis because it's flooded in cortisol. If that sounds like something you can relate to this video is for you. A ketogenic diet has neurological benefits. Why do we have to eat such an enormous amount of food?
Complex science. Clear explanations. Class is starting now.
Hi. I'm Dr. Chris Masterjohn of chrismasterjohnphd.com. And you're watching Masterclass with Masterjohn. We are now in our 31st, I think, but who can count, lesson on the system of energy metabolism. And today we're talking about how gluconeogenesis is regulated by cortisol.
As you can see on the screen gluconeogenesis is kind of like saving all your money so that you can pay your kids' college tuition and they get a degree in English. Gluconeogenesis consumes 6 ATP to get glucose so that cells will do the reverse reaction, glycolysis, to generate only 2ATP. You spend 6 and the return on your investment is 2. Gluconeogenesis is a very expensive investment with a negative ROI. As we talked about in the previous lesson the day-to-day regulation of gluconeogenesis is primarily by the insulin-to-glucagon ratio and the energy status of the liver cells. Insulin inhibits gluconeogenesis because it's the signal that you have plenty of glucose. Glucagon stimulates gluconeogenesis because it's the signal that you don't have enough glucose. High energy status stimulates gluconeogenesis because gluconeogenesis is expensive and the liver can only afford to engage in it when it has enough energy reserves that it can meet its own needs, its needs for biosynthesis, and enough left over to make glucose. For the same exact reason low energy status inhibits gluconeogenesis. But if gluconeogenesis is something that can be extremely essential because all of the physiologically essential roles of glucose and yet is extremely expensive, that sounds like something stressful; and in fact stress hormones also regulate gluconeogenesis. Glucocorticoids, as their name implies, are powerful regulators of blood glucose. Glucocorticoids are steroid hormones and -oid, kind of like humanoid for example from a science-fiction film, means resembling, like, or taking the form of. And a steroid is something that resembles cholesterol because all the steroids are made from cholesterol. A corticoid is a steroid that's produced by the adrenal cortex, which is the outside layer of the adrenal glands. It's a glucocorticoid because its primary purpose is to increase blood glucose. In humans the predominant and most powerful glucocorticoid is cortisol. Cortisol has a number of actions on blood glucose concentrations that are all geared towards increasing the availability of glucose to the brain. For example cortisol acts on the liver to increase gluconeogenesis and to increase glycogen storage. So remember that the liver is storing glycogen for the purpose of increasing blood glucose at a future time. So the liver is both, under the influence of cortisol, increasing the production of glucose for output into the blood and taking the excess of what is newly produced to store it as glycogen so that after these effects wane the liver is still very well primed to further increase blood glucose with its extra glycogen. In the muscle, cortisol decreases glucose uptake, decreases glucose utilization, and increases protein degradation. That means that the muscle will conserve its use of glucose for the blood so that the increased blood glucose can reach the brain.
Meanwhile the increased proteindegradation in the muscle frees amino acids from those proteins to go to the liver and to become substrates for gluconeogenesis. At adipose tissue, cortisol decreases glucose uptake and utilization and increases lipolysis; that releases free fatty acids. Those free fatty acids can now be used by other tissues such as the muscle in place of glucose so that the glucose can increase in the blood and become available to the brain. That even includes the liver because, if free fatty acids go to the liver and amino acids go to the liver, the free fatty acids can focus on providing the liver with the extra energy it needs to make glucose, meanwhile the amino acids become the building blocks for that glucose. It also acts acutely on the pancreas to decrease insulin and to increase glucagon, although chronic exposure of the pancreas to cortisol can actually, in the future, increase insulin output. Altogether this serves, whether by hormonal reasons, or because of the release of substrates from muscle and adipose tissue for gluconeogenesis, or by conserving glucose utilization in all the tissues except liver and allowing the liver to ramp up its glycogen storage and its glucose output; all of these converge on increasing blood glucose and making it more available to the brain. Because the brain is primarily sucking out glucose using glucose transporters that are simply extracting whatever happens to be floating in the blood in proportion to the concentration that's floating in the blood, so the only way to drive extra glucose into the brain is to increase blood sugar levels.
In order to understand how cortisol operates we should review gene expression from biology, something we actually haven't covered here yet. I should note now that insulin and glucagon and many of the other things that we've been talking about do regulate gene expression and we haven't talked about that yet.

We'll talk more about that in the long-term adaptations to diet once we are able to tie everything together in this course. The reason it's important to talk about with respect to cortisol is that unlike glucagon and insulin, which have acute effects on phosphorylation cascades and such immediate pathways, cortisol has all of its known effects through mechanisms that require protein synthesis. So if we want to take the information in DNA and turn it into a protein this in general is what has to happen. In the nucleus is where the DNA is, we have a process called transcription that makes an RNA template from that information in the DNA. The RNA leaves the nucleus and in a process called translation it feeds into a ribosome, which is made of a different type of RNA that plays structural roles to make the ribosome, and it feeds into the ribosome, the ribosome takes that information and makes a protein with it. The ribosomes are in the membrane of the endoplasmic reticulum, the RNA is on the outside, the protein comes out on the inside, if it needs modification that happens in the endoplasmic reticulum, maybe it goes onto another organelle called the Golgi apparatus, but in any case the protein can be made and simply exported from the ER -- the endoplasmic reticulum, not the emergency room -- once it's gone through the process of translation. Some people may point out to help remember these things that transcription means to simply copy something, translation means to go from one language to another; so an analogy that people often use to remember this is that DNA and RNA are both made of nucleic acids. So they're like different variants of the same nucleic acid language, whereas protein is something fundamentally different. So you're taking whatever information is in the DNA and the RNA and you're translating it in to this fundamentally different language of protein. Genes need to respond to signals in the environment. So every gene can be roughly broken down into its coding region, shown on the right, and it's promoter region, shown on the left. The coding region is what contains the information needed to assemble the proper amino acid sequence to make the protein.The promoter region consists of structures called response elements, abbreviated here RE, and these response elements respond to signals in the environment. This is actually a continuous strand of DNA and as far as the gene is concerned there's no difference between one region and the other. We humans look at what happens and we say, "hey everything from here on is coding for amino acids, everything before here contains sequences that respond to the environment." But actually this is just one nucleic acid after another, one nucleic acid after another perfectly continuous down this line. One of the many response elements that are in the promoter regions of genes is the glucocorticoid response element abbreviated here as GRE. If the GRE is in the promoter region of a specific gene then that gene is a glucocorticoid- responsive gene because the GRE in its promoter region allows that gene to respond to glucocorticoids. Unlike insulin, which binds to a cell surface receptor and carries out a cascade of reactions that occur inside the cell, all the while insulin remains outside the cell binding to the receptor, unlike that situation, cortisol has to enter the cell and even get into the nucleus. The glucocorticoid receptor is normally present in the cytosol and it's bound to a chaperone protein called Hsp90, which stands for heat shock protein 90.

This is part of a class of proteins that are known to respond to heat stress, but this particularly well characterized binding is primarily a way to allow the glucocorticoid receptor to respond to cortisol. In the absence of cortisol the glucocorticoid receptor stays bound to Hsp90 and it stays in the cytosol. And a gene with a glucocorticoid response element in its promoter region inside the nucleus will not be expressed. By contrast, if the cortisol enters the cell and it binds to the glucocorticoid receptor, that causes the dissociation of the cortisol receptor complex from Hsp90. That allows cortisol in the glucocorticoid receptor to enter into the cell and to bind to the promoter region of genes that are responsive to glucocorticoids. That will allow the information in the DNA to be turned into RNA. Now it should be noted I've simplified this here by showing the DNA getting expressed upon binding to the receptor, but it's not true that the response elements always bind to something in order to express the gene. Sometimes the gene is expressed in the absence of something binding to it, and when that binding occurs it actually suppresses it. What we'll say here in general is that the presence of a GRE in the promoter region of specific genes makes those genes glucocorticoid-responsive genes. The binding of cortisol to the glucocorticoid receptor releases the receptor from Hsp90, allows it to go into the nucleus, bind to the GRE within the promoter region of glucocorticoid-responsive genes and thereby regulate the transcription of those genes. The profile of proteins that are produced under the influence of cortisol have two major impacts on gluconeogenesis. The first is that some of these proteins antagonize insulin's phosphorylation cascade. That means in the presence of insulin more cortisol will stop the activity of that insulin. So it induces a state of relative insulin resistance. Since insulin suppresses gluconeogenesis the insulin resistance caused by cortisol promotes gluconeogenesis. Meanwhile cortisol also directly regulates gluconeogenic enzymes. Among those increased are PEPCK, fructose 1,6-bisphosphatase, which catalyzes one of the final steps in gluconeogenesis, the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate. It stimulates fructose 2,6-bisphosphatase, which catalyzes the degradation of fructose 2,6-bisphosphate, the regulatory molecule that stimulates glycolysis and inhibits gluconeogenesis. It stimulates glucose 6-phosphatase and the glucose 6-phosphate transporter that allows glucose 6-phosphate to get in the endoplasmic reticulum where it has access to glucose 6-phosphatase, which catalyzes the conversion of glucose 6-phosphate to free glucose. That's the truly final step in gluconeogenesis in the liver and its role is to allow that glucose to become free and enable it to leave the liver and go into the blood. So from the beginning through the end cortisol is increasing the expression of the gluconeogenic enzymes. And in doing that it increases the total capacity for gluconeogenesis and it amplifies any other pro-gluconeogenic signaling. In other words, if insulin and glucagon interact to suppress or stimulate gluconeogenic enzymes that are already produced, and cortisol increases the amount of those enzymes, then whatever insulin or glucagon does to gluconeogenisis is amplified by the fact that your total capacity for gluconeogenesis is increased. For example if you increase the total capacity for gluconeogenesis two-fold and if you have a low insulin-to-glucagon ratio, you could potentially get double the impact than you could without cortisol increasing the expression of those genes. In sum cortisol is a molecule that represents the stress response, the need for more glucose, unlike insulin and glucagon, which are primarily responding to the normal level of blood glucose. If you have high cortisol in a fight-or-flight response it may be because you need higher blood glucose than normal in order to meet the demands of that stress response. That would be a glucose-demanding stress. However, hypoglycemia is also a stress in itself. Hypoglycemia could be caused, for example, on the one hand, by poor blood sugar regulation. In some cases if you eat a carbohydrate load that you can't handle because your regulation of that load is messed up and that provokes you into hypoglycemia, then that hypoglycemia could provoke a cortisol response. It shouldn't, because when the regulation is happening naturally insulin and glucagon are fully capable of doing what they need to do to regulate blood sugar. But if you go into hypoglycemic stress, that means there's something wrong with that first layer of regulation and you need to tap into the second layer of the stress response. But it could also simply be glucose deprivation. At least in theory if there's some level of glucose deprivation that goes beyond the ability of insulin dropping and glucagon rising to normalize your blood sugar then that itself could potentially lead to the hypoglycemic stress that elicits the cortisol response. The end result is that cortisol is there as a backup mechanism to acutely promote and also amplify all the other signaling, to stimulate gluconeogenesis out of necessity. Because remember this is an energetically expensive process that only makes sense to do when you have to. So let's look at a handful of studies about whether carbohydrate restriction could provoke a cortisol response. I want to emphasize that I'm just going to show you three studies and this is not an exhaustive review of the literature. But the literature in general is inadequate and to my knowledge we're not skipping over anything that would offer any kind of definitive conclusions about any of this, certainly no conclusions that are contrary to the ones that I'm going to make in this presentation. Here's data from rheumatoid arthritis patients who were given a weight-appropriate ketogenic diet, meaning not designed for any kind of fat loss, and they didn't report the exact percentage calories or exact nutrients in the diet, but we can approximate that it was about 80% calories as fat. They were given this for seven days and then they were re-fed for two weeks on a lacto-ovo-vegetarian diet. The authors said that the purpose of the lacto-ovo-vegetarian diet was to act as a kind-of-sort-of placebo in the sense that the patients were told that both of these were experimental diets and that allowed them to essentially trick the patients into thinking that either of them had potential to treat their disease. And what you see here is that after seven days on a ketogenic diet there's a statistically significant increase in blood cortisol. It was about a relative increase of 15% or 14%. After they were re-fed on two weeks of the lacto-ovo- vegetarian diet it went back down to baseline. This was not randomized, it was a before-and-after study, but it supports the idea that carbohydrate restriction at least across seven days is going to increase cortisol levels because insulin and glucagon modulation isn't enough to maintain blood glucose at what they need to be. Here's data from nine children with epilepsy who were put on the traditional four-to-one ketogenic diet, which refers to the amount of fat versus non-fat mass in that diet, and this provides approximately 90% of calories as fat. Again they didn't report those details in the paper, but these diets typically provide about that much. This was for the purpose of seizure control; this is the well-established method of seizure control in children with epilepsy that doesn't respond to drugs. They were on the diet for three to four weeks and you can see there was again a statistically significant increase in cortisol levels. In this case the increase was almost 4 times larger than it was in the previous study. Let's come back to why there might have been differences in the cortisol response to the ketogenic diets after we look at a third study. This data is from a radically different population. These people are not only not sick but they're competitive off-road cyclists. Eight of them underwent a randomized crossover study involving four weeks of a ketogenic or a mixed diet. That means that everyone got both diets, but some got the ketogenic diet first others got the mixed diet first. After they were on each diet for four weeks continuing on that diet they cycled on an ergometer with progressively increasing intensity until they reached maximal effort. In other words, as you see rest, 45 minutes, 90 minutes, max effort, what they're doing is they measure the data that's shown on the screen before they start the trial, then they cycle for 45 minutes. Through that 45 minutes they're progressively increasing the intensity, they keep going for 90 minutes, at 90 minutes they've not only gone twice as long, but they're also going at a much higher intensity, and eventually they get to max effort, which is when they reach, what it sounds like, the absolute maximum that they're able to tolerate. And these diets were, on the ketogenic diet, 70% fat by calories and on the mixed diet 30% fat. If you look at what happened to cortisol... I should note among the things that I don't like about the reporting of the data in this study, they did not look at statistical significance between each of the groups at each of the time points; instead they looked at the significance overall to say that through this data there are differences. That's not statistically rigorous, but it is what it is. So the cortisol was either not different or slightly higher on the mixed diet than the ketogenic diet at rest. That flips around when they start exercising. You can see that during exercise the cortisol levels are lower, but on the ketogenic diet they have higher cortisol levels than the mixed diet. That's also true as you get to minutes. Then as you get to maximum effort that difference pretty much disappears. So it seems like at rest these extremely healthy competitive athletes, who, by the way, as we covered in lesson 17 and 18 are doing exercise that should be largely fat adaptable. These athletes seem to be meeting their needs for carbohydrate on the ketogenic diet at rest, which suggests at least from the cortisol response that they are meeting those needs to maintain their blood glucose at normal because of the natural regulation you'd expect of insulin and glucagon. They didn't measure glucagon in the study, but you can see that at rest insulin levels are 19 on the mixed diet and 10 on the ketogenic diet. So insulin basically drops in half to maintain the same level of blood glucose. That could be partly mediated by glycogen release or partly mediated by gluconeogenesis, probably a little bit of both. When they start exercising the muscles need more glucose. And you can see that the blood glucose starts to rise in each of these cases, insulin levels drop in both of them to the point where the mixed diet has hardly any more insulin than the ketogenic diet does. The changes in insulin and the glucagon that we don't see don't seem to be enough to sustain the increased need of the muscles for glucose during the exercise because upon exercising is when we see this ratio flip around and the cyclists on the ketogenic diet having higher cortisol than they did on the mixed diet. This continues at 90 minutes. The glucose in the blood drops back down to about basal levels, perhaps because the output of glucose isn't quite keeping up with the uptake of glucose to keep it any higher than basal levels as it was at minutes. But presumably you have a lot more glucose utilization in the muscle, a lot more glucose output, but they're balanced and so the blood sugar is staying pretty even. Insulin is maybe a little bit lower, about the same in both groups, about the same as it was at minutes. Cortisol is a little higher in each group and it's again higher on the ketogenic diet. At maximum effort that difference seems to even out, cortisol is the highest as it was across the entire thing, perhaps because at that point needs for blood glucose are maximal and no one on any diet can't exert maximal effort with no spike in cortisol. And you can see that the spike in cortisol is driving blood glucose up to 120 and that is maintained partly by these relatively high levels of cortisol compared to the earlier time points at 45 and 90 minutes. At maximal effort that seems to be the place where the high demand for glucose, because of the exercise, is becoming the dominant factor in cortisol beyond anything about the insulin-to-glucagon ratios and the glycogen levels in the ketogenic diet versus the mixed diet. So if you look at this study it seems like in healthy people who are very well trained you may not see a spike in cortisol on a ketogenic diet except in the cases where the exercise drives up the need for glucose. Now we have to be really careful with interpreting these studies. So, for example, let's look at the carbohydrate and fat contents of the diet. The first study we looked at derived 80% of calories as fat and it showed a moderate increase in cortisol. The second study that we looked at derived 90% of the calories as fat and it showed a much larger, almost four times larger, spike in cortisol. The last study that we looked at showed that cortisol didn't spike except when exercise was increasing the demand for glucose, but it derived only 70% of its calories as fat, the least out of any of these studies. On the other hand the first study involved rheumatoid arthritis patients. These people are sick with an inflammatory disorder. The second study involved children with epilepsy that was resistant to drugs. These children have severely disturbed physiology that puts them into such an energetic crisis that without this treatment they have seizures. The third study involved healthy competitive off-road cyclists. These people don't just not have diseases; they engage in physical performance that puts them in top shape, especially with respect to energy metabolism. So are these studies coming to conflicting results because of the health of the people involved? Do significant health problems raise the need for blood sugar or the need for cortisol in some way that precipitates, or allows, enables the ketogenic diet to provoke that increase in cortisol? Or is this all about the degree of carbohydrate restriction? Do the ketogenic dieters with epilepsy have the strongest increase in cortisol because their situation demands the most intense ketogenic diet out of any of these and the greatest degree of carbohydrate restriction? Do the patients with rheumatoid arthritis have a less pronounced cortisol spike because their glucose restriction was less pronounced? Do the off-road cyclists have the least evident spike in cortisol out of anything that only becomes clear during exercise because they're healthy or because they had the most moderate ketogenic diet that was the least intense in its glucose restriction out of all three? These are questions that we can't answer because we just don't have a lot of data on the cortisol response to glucose restriction. It makes sense to me that if the glucose restriction gets intense enough it's likely to induce an obligate increase in cortisol if the insulin and glucagon modulations just aren't enough to handle the degree of restriction that you're imposing on your system. I can't support that because there's too many studies with different methodologies that don't clearly control those variables. I also believe that if you're less healthy and you have other taxes on your energy supply or other things going on in your body that are contributing to inflammation or obesity or other derangements of normal physiology; other things that are totally normal but are stressors like pregnancy, like work stress, like family stress, anything that goes into your stress bucket; then maybe the addition of all the things into your stress bucket makes glucose restriction going on top of it, if that's the thing that makes it overflow, then maybe that's what would also put you into the cortisol response. In any case we can see from these studies that glucose restriction in and of itself does not always regardless of context increase cortisol. However, there may be a degree of glucose restriction, particularly as you get down to 10 to 20% of calories, where you cross a threshold that does require an obligate increase in cortisol. And it's at least true that in the context of other stressors on the system many people will experience a rise in cortisol, indicating a stress response, in response to carbohydrate restriction. Cortisol is called a glucocorticoid because it is a powerful regulator of gluconeogenesis. And it makes sense that the stress response is a powerful regulator of gluconeogenesis because gluconeogenesis is an energetically expensive investment with a negative ROI that it only makes sense to engage in if there's a real need for it. The audio of this lesson was generously enhanced and post-processed by Bob Davodian of Taurean Mixing, giving you strong sound and dependable quality. You can find more of his work at taureanonlinemixing com. If you want to keep watching these lessons you can find them on my YouTube at youtube.com/chrismasterjohn. Or on my Facebook page at facebook.com/chrismasterjohn. Or you can sign up for MWM Pro to get early access to content, enhanced keyword searching, self-pacing tools, downloadable audio and transcripts, a rich array of hyperlinked further reading suggestions and a forum for each lesson to get a sense of community and ask questions of each other and me. If you really want to own these lessons, study them, and get the most out of them, you can sign up for MWM Pro at chrismasterjohnphd.com/pro. All right, I hope you enjoyed this lesson. Signing off, this is Chris Masterjohn of chrismasterjohnphd.com. You've been watching Masterclass with Masterjohn. And I will see you in the next lesson.


Интересно? Будем не спеша переводить...
Потери в деньгах вызывает у вас беспокойство? Так же, вероятно, чувствует себя ваша печень, когда она участвует в глюконеогенезе, потому что она тонет в кортизоле. Если это как то вас беспокоит, то видео для вас.
Кетогенная диета имеет явные неврологические преимущества. Почему мы должны есть такое огромное количество пищи?
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Здравствуй. Я доктор Chris Masterjohn из chrismasterjohnphd.com. И вы смотрите мастер-класс с Masterjohn.
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А сегодня мы будем говорить о том, как глюконеогенез регулируется кортизолом.
Как вы можете видеть, глюконеогенез похож на вклад ваших денег в учебу своих детей, чтобы они получили диплом по английскому языку. Глюконеогенез потребляет 6 АТФ для получения глюкозы, а клетки будут делать обратную реакцию - гликолиз, чтобы сгенерировать только 2 АТФ. Вы тратите 6, а доход от ваших инвестиций - 2. Глюконеогенез - очень дорогая инвестиция с отрицательной рентабельностью. Как мы говорили на предыдущем уроке, ежедневное регулирование глюконеогенеза в основном связано с соотношением инсулин-глюкагон и энергетическим состоянием клеток печени. Инсулин ингибирует глюконеогенез, получая сигнал о том, что у вас много глюкозы. Глюкагон стимулирует глюконеогенез, получая сигнал, что у вас недостаточно глюкозы. Для глюконеогенеза требуются высокие энергетические затраты, потому что глюконеогенез дорог, а печень может позволить себе заниматься только тогда, когда она обладает достаточными запасами энергии для того, чтобы удовлетворить свои потребности в биосинтезе и ещё останется, чтобы сделать глюкозу. По той же самой причине низкий уровень энергии подавляет глюконеогенез.
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Но и стрессовые гормоны также регулируют глюконеогенез.
Глюкокортикоиды, как следует из их названия, являются мощными регуляторами глюкозы в крови. Глюкокортикоиды - это стероидные гормоны и оконачание -иоды, вроде как гуманоиды, например, из научно-фантастического фильма, означает "напоминающий" или "принимающий форму". А стероид - это нечто похожее на холестерин, потому что все стероиды сделаны из холестерина. Кортикоид - это стероид, который вырабатывается "корой" надпочечников, т.н. наружным слоем надпочечников. У глюкокортикоида основная цель - увеличить уровень глюкозы в крови.
У людей преобладающим и самым мощным глюкокортикоидом является кортизол. Кортизол имеет ряд действий по концентрации глюкозы в крови, которые направлены на увеличение доступности глюкозы в мозг. Например, кортизол действует на печень для увеличения глюконеогенеза и увеличения содержания гликогена. Поэтому запомните - печень хранит гликоген с целью регуляции уровня глюкозы в крови. Таким образом, печень, одномоментно, под воздействием кортизола, увеличивает выработку глюкозы для выброса ее в кровь, а если глюкозы избыточное количество, то она сохраняется избыток в виде гликогена, так что после того, как кол-во глюкозы уменьшится, печень будет все еще очень хорошо "затарена" для возможного, в дальнейшем, повышения уровня глюкозы в крови с помощью гликогена.
В мышцах кортизол снижает поглощение глюкозы, уменьшает ее использование и увеличивает разрушение белка. Это означает, что мышцы не будут использовать глюкозу, сохраняя ее уровень таким, чтобы в достаточной мере обеспечивать мозг энергией.
Между тем повышенная деградация белков в мышце освобождает аминокислоты из этих белков для того, чтобы попасть в печень и стать субстратами для глюконеогенеза. В жировой ткани кортизол снижает поглощение и использование глюкозы и увеличивает липолиз, который высвобождает свободные жирные кислоты. Эти свободные жирные кислоты могут теперь использоваться другими тканями, такими как мышцы, вместо глюкозы так, что глюкоза может увеличиваться в крови и становиться доступной для мозга. Это так же включает в себя и печень потому, что если свободные жирные кислоты поступают в печень и аминокислоты попадают в печень, свободные жирные кислоты могут сосредоточиться на обеспечении печени дополнительной энергией, необходимой для производства глюкозы, между тем аминокислоты превращаются строительные блоки для этой глюкозы. Кортизол также активно действует на поджелудочную железу, чтобы уменьшить инсулин и увеличить глюкагон, хотя хроническое воздействие кортизола может в будущем увеличить выработку инсулина. В целом это служит для глюконеогенеза либо для сохранения глюкозы от использования в тканях, кроме печени, что позволяет печени наращивать хранение гликогена и выработку глюкозы; все они служат для повышении уровня глюкозы в крови и делают ее более доступной для мозга. Мозг, в первую очередь, "высасывает" глюкозу с помощью переносчиков глюкозы, которые просто извлекают все, что содержится в крови, пропорционально градиенту концентрации, поэтому единственный способ стимулировать дополнительную глюкозу в мозг - увеличить уровень сахара в крови.
Чтобы понять, как работает кортизол, мы должны рассмотреть экспрессию генов из биологии, чего мы на самом деле еще не рассмотрели. Теперь я должен отметить, что инсулин и глюкагон и многие другие вещи, о которых мы говорили, регулируют экспрессию генов, и мы еще не говорили об этом.

Мы поговорим об этом в долгосрочной адаптации к диете, как только мы сможем связать все вместе в этом курсе. Причина, по которой важно говорить о кортизоле, заключается в том, что в отличие от глюкагона и инсулина, которые оказывают острое влияние на каскады фосфорилирования и такие непосредственные пути, кортизол обладает всеми своими известными эффектами с помощью механизмов, которые требуют синтеза белка. Поэтому, если мы хотим взять информацию в ДНК и превратить ее в белок, это в общем-то и должно произойти. В ядре находится ДНК, у нас есть процесс, называемый транскрипцией, который делает шаблон РНК из этой информации в ДНК. РНК покидает ядро ​​и в процессе, называемом трансляцией, он питается рибосомой, которая состоит из другого типа РНК, которая играет структурные роли, чтобы сделать рибосому, и она питается в рибосому, рибосома принимает эту информацию и делает белок с ним. Рибосомы находятся в мембране эндоплазматического ретикулума, РНК находится снаружи, белок выходит изнутри, если ему нужна модификация, которая происходит в эндоплазматическом ретикулуме, возможно, он переходит на другую органелл, называемую аппаратом Гольджи, но в в любом случае белок можно сделать и просто экспортировать из ER - эндоплазматический ретикулум, а не в отделение неотложной помощи - как только он пройдет процесс перевода. Некоторые люди могут указать, чтобы помнить об этих вещах, которые транскрипция означает просто скопировать что-то, перевод означает переходить с одного языка на другой; поэтому аналогия, которую люди часто используют, чтобы запомнить это, состоит в том, что ДНК и РНК оба сделаны из нуклеиновых кислот. Таким образом, они похожи на разные варианты того же языка нуклеиновых кислот, тогда как белок - это нечто принципиально иное. Таким образом, вы принимаете любую информацию в ДНК и РНК, и вы переводите ее на этот принципиально другой язык белка. Гены должны реагировать на сигналы в окружающей среде. Таким образом, каждый ген может быть грубо разбит на свою область кодирования, показанную справа, и это область промотора, показанная слева. Кодирующая область - это то, что содержит информацию, необходимую для сборки правильной аминокислотной последовательности, чтобы сделать белок. Область промотора состоит из структур, называемых элементами ответа, сокращенно здесь RE, и эти элементы ответа реагируют на сигналы в окружающей среде. Это на самом деле сплошная цепь ДНК, и, насколько это касается гена, нет разницы между одним регионом и другим. Мы, люди, смотрим, что происходит, и мы говорим: «Эй, все здесь, это кодирование аминокислот, все, что здесь есть, содержит последовательности, которые отвечают окружающей среде». Но на самом деле это всего лишь одна нуклеиновая кислота за другой, одна нуклеиновая кислота после другой совершенно непрерывна по этой линии. Одним из многих элементов ответа, которые находятся в областях промотора генов, является элемент ответа глюкокортикоидов, сокращенный здесь как GRE. Если GRE находится в промоторной области определенного гена, то этот ген является гликокортикоид-чувствительным геном, потому что GRE в его промоторной области позволяет этому гену реагировать на глюкокортикоиды. В отличие от инсулина, который связывается с рецептором клеточной поверхности и выполняет каскад реакций, которые происходят внутри клетки, все время, пока инсулин остается вне клеточной связи с рецептором, в отличие от этой ситуации, кортизол должен проникнуть в клетку и даже попасть в клетку ядро. Глюкокортикоидный рецептор обычно присутствует в цитозоле и связан с белком-шапероном под названием Hsp90, который представляет собой белок 90 теплового шока.
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Последний раз редактировалось Nikolaivanych; 30-01-2018 в 04:14.. Причина: Переводим, последняя часть не для слабонервных :)))
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