Fasting (Post-absorptive state) | Metabolism

hi everybody dr mike here in this video i want to talk to you about the post-absorptive or fasting state this is characterized by a decrease in blood glucose levels and how the body responds to increased blood glucose levels now you may be thinking why do we focus on glucose why aren't we focusing on fats and proteins and the answer to that question is because glucose is the most important energy substrate for organs such as our brain for example our brain only wants carbs for energy now if you think about other energy sources like proteins and fats and their derivatives like amino acids fatty acids glycerol they all feed into the processes that can turn into glucose or a glucose substrate for energy so we need to look at glucose itself firstly normal glucose levels so i'm going to write glucose like this normal glucose levels sit between four to six millimoles per liter this is where we want it to sit if it goes too low blood glucose levels dropping too low we need to increase it if it goes too high we need to bring it back down what we're going to talk about today is what happens after extended periods of time of not eating what we call fasting or the post-absorptive state this can be between meals so between four to eight hours or it could even be longer for example when we wake up in the morning after not eating for about 10 to 12 hours what's happening in our body to maintain our blood glucose levels between four to six all right so first thing is this i wake up in the morning i'm the i'm a 70 kilogram male i have my liver for example and in my liver we have cells called hepatocytes which do all the metabolic processing and a whole bunch of other things and there's the mitochondria as well which plays a really important role of producing energy from our micronutrient substrates we've got our pancreas which we need to talk about here and we've also got muscle tissue and adipose tissue as well all of these organs and structures are playing a role in maintaining blood glucose levels so i've just woken up as a 70 kilogram male i have around about 80 grams of glycogen stored in my liver now firstly glycogen is the stored form of glucose so glucose being a simple sugar if we don't want to use it to make energy or atp we click it together like lego blocks to produce glycogen and our liver is our primary storage site for glycogen our kidney also stores some glycogen that we can use and i may talk about that in a little bit so i've got about 80 grams of glycogen stored in my liver and i start to break it down again i'm not eating it's been 10 to 12 hours and i haven't eaten a thing this glycogen what can happen is it can break down into something called glucose 6-phosphate and glucose 6-phosphate can reversibly turn into glucose via an enzyme called glucose 6-phosphatase and that turns into glucose glucose can then leave the bloodstream and increase our blood glucose levels but how does this happen how do we take stored glycogen break it down into glucose to be released in the bloodstream this is where the pancreas comes into play because if our blood glucose levels begin to drop the blood supply that feeds the pancreas stimulates a certain type of pancreatic cell called an alpha cell and these alpha cells they produce a hormone called glucagon now what glucagon does is it stimulates this process glucagon can stimulate glycogen so if it ends in ogen remember it means stored in an active that's how you remember glycogen as being the stored and active version of glucose glucagon when the blood glucose levels are low so that's its stimulus it's stimulus is when there's a drop in blood glucose levels glycogen breaks down glucose 6-phosphate glucose 6-phosphatase turns it to glucose it can then be shuttled out of the hepatocyte into the bloodstream and be delivered to the tissues of the body but now think about this now the glucose released into the bloodstream what happens to the blood glucose levels it starts to go up a little bit we don't want to just continually break down that stored glycogen right because our blood glucose levels will go too high so the increase in blood glucose will travel again to the pancreas and this time trigger another cell type called a beta cell and the beta cells produce something called insulin and like i said this is now triggered by an increase in blood glucose what does insulin do in this process insulin again travels to the hepatocyte of the liver and it's a negative regulator glucagon was a positive regulator glucagon stimulated this process insulin inhibited so now that insulin's been released it stops this from happening blood glucose levels start to drop if it drops glucagon stimulates goes too high insulin inhibits can you see that this is maintaining a happy healthy balance this whole process here that we've just spoken about for the breakdown of glycogen into glucose ultimately this is called glycogenolysis glyco which basically means glycogen there's glycogen lysis meaning splitting apart or breaking apart this is the breaking part of glycogen into glucose to make energy so this is how we first begin to increase our blood glucose levels however i only have 80 grams of stored glycogen over time if i don't eat i will use eight percent of my stored glycogen from my liver every hour now the kidneys also contribute the kidneys contribute around about 10 percent in this process so don't forget the kidneys don't discount them kidneys contribute 10 percent of glycogen storage to the utilization to produce glucose in this process but after 10 to 12 hours of doing this and not eating my glycogen stores are gone so how do i maintain blood glucose levels all right this is where another process comes into play which is called gluconeogenesis once i've used up my glycogen the blood glucose levels start to drop again glucagon is stimulated insulin is inhibited it's low glucagon is high and what glucagon can do is it can travel to distant tissues so glucagon now can travel via the bloodstream to the muscle glucagon can travel via the bloodstream to the fat and what it does is it's a positive regulator of two important processes the first process here is proteolysis or proteolysis in muscle what this does is it takes protein and breaks it down into amino acids one really important amino acid in this process which i'll talk about is alanine but there are other amino acids what we call gluconeogenic amino acids that contribute to this so glucagon stimulates this now think about this if insulin is released into the bloodstream doesn't matter how much even if it's a little bit this is significantly inhibited so we need to have low blood glucose levels and low blood insulin levels in order for glucagon to stimulate muscle to break down protein into amino acids and to stimulate fat or lipids or triglycerides to be broken down into fatty acids and glycerol because as we know triglyceride three fatty acids one glycerol so now what we've done is we've used up our glycogen insulin levels are low glycogen levels glucagon levels are high proteolysis has been stimulated amino acids are released like alanine what we've got here i didn't talk about it is called lipolysis i should probably say lipolysis which is the splitting apart of triglycerides into fatty acids and glycerol have been released and now what happens again what's the whole point increased blood glucose levels so what happens here glycerol can jump into this process and it can reversibly turn into glucose it can jump into this process here now this process which i haven't yet spoken about is called glycolysis glycolysis is taking glucose to produce atp the opposite of what we're talking about here right glucose turning into atp glucose goes to glucose 6-phosphate glucose 6-phosphate turns into pyruvate through a number of steps which i haven't mentioned pyruvate can jump into the mitochondria turn into acetyl-coa and through the krebs cycle also known as the citric acid cycle can produce a whole number of products it produces nadh it produces carbon dioxide these products go specifically the nadh go to the electron transport chain to produce a whole bunch of atp for energy but we can hijack this system and make it go backwards to produce glucose to increase blood glucose levels so glycerol can jump into the glycolytic pathway go backwards because that's what's happening ultimately turn into glucose 6-phosphate turn into glucose jump out so glycerol from triglycerides can increase blood glucose levels all right that's the first point alanine what can alanine do alanine let's write it in red can turn into pyruvate now pyruvate is irreversible it can't go back to glucose 6-phosphate so how do we use alanine to produce glucose if we can't go backwards well pyruvate can turn into oxaloacetate and if pyruvate turns into oxaloacetate oxaloacetate can leave the system ultimately turn into glucose 6-phosphate which is turning into glucose brilliant so through this process amino acids such as alanine not all amino acids but alanine specifically turn into pyruvate pyruvate turns into oxaloacetate leaves the krebs cycle can jump back into this glycolytic pathway but go backwards turn to glucose 6-phosphate and increase blood glucose levels fatty acids fatty acids can jump into the system and turn into acetyl coa now i want you to think about this if this process of proteolysis or proteolysis and lipolysis have been stimulated what will happen is these amino acids that have been utilized diminish the amount of oxaloacetate because they're turning into pyruvate which is turning into oxaloacetate and that's leaving the system now oxaloacetate is a substrate that needs to bind to acetyl coa to produce atp but what's happening here is fatty acids are turning into acetyl co acetyl coa so acetyl coa levels are going up oxaloacetate levels are going down because they're leaving to turn into glucose so there's a mismatch oxalicity just starts to increase increase increase increase it can't bind to oxaloacetate so what happens when all this acetyl coa increases too much well they turn into ketones and so acetyl coa there's not much room here will turn into ketones and ketones can leave the system to again be utilized as an energy substrate how because it jumps back into this process and it can be used to produce atp ketones all right something else lactate we can use lactate as a substrate in this process and so lactate can come in and turn into pyruvate and again pyruvate oxaloacetate turn into glucose so this process called gluconeogenesis now there's no room to really write it up here but let's put it down here gluconeogenesis gluco neo genesis takes all of these non-carbohydrate-based sources so what were they so it's amino acids like alanine it's fatty acids it's glycerol it's lactate and takes them and utilizes them to produce glucose increase in blood glucose levels insulin like i said is a strong negative regulator of gluconeogenesis and after 10 to 12 hours gluconeogenesis is contributing to 50 of all the glucose that's being released into our bloodstream because like i said every hour eight percent of my glycogen is being utilized until there's hardly any or none left at all so what we're talking about here is gluconeogenesis glycogenolysis to ultimately increase blood glucose now the final point i need to make here is that it's not just glucagon that stimulates this there are other hormones or chemicals that are released in the body that can contribute to increasing blood glucose levels in times of fasting what are these hormones and chemicals noradrenaline adrenaline cortisol growth hormone and thyroid hormones they are also strong strong agonists to promote this process of gluconeogenesis specifically glucagon and adrenaline so adrenaline is the sympathetic nervous system fight or flight right so glucagon and adrenaline they're fast acting they do this immediately but cortisol growth hormone thyroid hormones they're more slow acting they take time and they can have their effects over a longer period so this is a quick run through what happens metabolically to your body in the post-absorptive or fasting state

Channel: Dr Matt & Dr Mike

Views: 12,004

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Length: 15min 35sec (935 seconds)

Published: Sun Aug 16 2020