Diabetes & Mitochondria: How Nutrition Connects the Two. [Study 32]

hi hello welcome to physionic welcome to a physionic long-form video i'd actually recorded this video about two days ago but uh going through it and honestly just uh honestly just as i was recording it i was really noticing how low energy i was and not that that's necessarily a problem but beyond that uh how scattered my mind was as i was recording and i thought to myself well nick you can't release this kind of crap content out there i mean the information was solid but uh the way i was presenting it just wasn't just kind

of was all over the place so hopefully round two this time around i found some time to to record it again so hopefully this will be a a little more succinct it'll still be a long video but it'll be a little more succinct a little more on pace and on track with uh with what we're going to be discussing today and today's discussion is actually going to be related to it's going to be a part 2 to the previous video that i released last week and i mentioned a series of effects that happened to mitochondria

or mitochondrial behavior when we have changes in the nutrient environment of our cells so i describe starvation fast and starvation which aren't quite the same but in the scenario that we talked about i tried to touch on both a little bit mainly on starvation and over nutrition now in this podcast i'd like to discuss that a little bit more but more specifically towards over nutrition and diabetes specifically and the information that i'll be going over here is actually the same from the same review scientific review as the last one now i received a few questions

uh related to that scientific review people are asking if they did uh if this information came from studies because i'm not going to be showing you any data i'm just going to be showing you graphics and stuff they were asking if this information was coming from human trials and because it's a scientific review uh it's going to be coming from multiple sources so from cell studies from animal studies and from human studies so i can't really parse out you know what little tidbit of information they got from one source or another but i do have

the uh article the study linked or the review linked for you as well as my notes in the margins so it makes it much easier to to read if you don't actually want to read the entire review itself i break it down so i'll create like a paragraph that covers like three pages of information that the researchers mentioned so that's something also i i guess at the end of this so i'm gonna break this up into i suppose like three separate portions i'm gonna discuss how diabetes how mitochondria and overnutrition affect diabetes or the the

development of diabetes in a mitochondrial specific way the second thing that i want to cover is a little bit on the mitochondrial morphology and a bit of a catch 22 when it comes to changes in mitochondrial shape related to uh over nutrition like in obesity and the third one i i can already predict one of the questions that's going to be in the comments is going to be related to can i fix this by fasting so i'll quick touch on that i'm not going to go into too much detail with that but i'll quick touch

on that because i i know a lot of you i know a lot of you really like fasting so i'm going to go ahead and try to answer that in in this podcast as well or in this video as well used to be a podcast still is but has its own version uh on audio all right with oh i suppose uh for those of you that don't know who i am as in you're new to the to the brand to physionic my name's nick uh my name is nicholas verhoeven i'm a phd candidate in molecular

medicine i work in a cell biology lab and i actually the cell biology lab that i work in which i'll actually be going to in about an hour and a half is a lab that works on mitochondria and autophagy so we're going to be touching on both of those topics in this video all right without further ado let's go ahead and jump through this all right so the question that we're examining is uh more related to diabetes diabetes and obesity's relationship to mitochondrial behavior and when i say behavior i've got these quotations because you know

this behavior isn't a choice it's a biochemical reaction that occurs to situations related to diabetes and and obesity as i'll explain this information again comes from this particular review the scientific review known as mitochondrial dynamics and the regulation of nutrient utilization and energy expenditure this comes from a highly highly reputable journal called cell metabolism this review is about eight years old at this point something like that so there's definitely going to be more information that's come out since this review released but this will still set a great groundwork for let's say 95 of the information

that's out there all right to give you a bit of background again if you've watched the first video uh you can skip this section but you know if you want a refresher i'll i'll certainly go through it i'm not going to go in as much detail so if you want more details certainly go over to the first video because i spent a good you know 10 minutes describing this but this is this is the way that we generate cellular energy or it's the primary way i should say that we develop cellular energy within our cells

and this may look complex but i've actually removed certain components so there's another membrane so another one of these right here so this is the inner membrane of the mitochondrion there's an outer membrane of the mitochondrion but i've removed that so we're looking at this inter-membrane space and the mitochondrial matrix and the inner membrane and embedded in that inner membrane are a series of different proteins we don't need to know what those proteins are but as a complex as a whole they're called the electron transport chain now the nutrients that you consume fats sugars when

they enter your cells what happens to them and again i've got visuals for this in the other video so hop on over to that one first but what happens to them is they get converted to intermediate molecules like pyruvate acetyl coa and then they eventually those two aren't important but what are important is the production of these right here nadh and fadh these then allow a powering again i'm generalizing because i want you to go over to the other one other video to to get the specifics but the powering of this electron transport chain the

reason why that's important is the electron transport chain the big point is that it pumps protons into the inter membrane space because that's where you want it you want this area the mitochondrial matrix to be more negative so you pump these positive ions out of or atoms out of the matrix into the inter membrane space this then allows the atp synthase as you can see by the arrow here the protons will then flow back into the matrix and this atp synthase will rotate it's kind of like a i likened it to a uh to a

water mill you know water that that flows over the mill and it starts to rotate the uh the the wheel the same thing happens here you get this rotation of the atp synthase and the end result then is the production of atp so that's really all you need to know that the the food stuff that you consume or if it's released from fat cells for example or if you have sugar that's released from the liver or sugar that's stuck as glycogen in the muscle cells or you know in the liver then you get the production

of nadh and fadh this powers the etc the electron transport chain which then allows protons to build up out here which then come moving through here it's just a cycle just goes back and forth back and forth all right now when the supply is really great so we're talking about an over consumption situation a person who suffers from potentially obesity type 2 diabetes or just generally overweight a person who's continuously gaining weight the supply is much greater than the demand so the cellular processes of our bodies is the demand so all the enzymatic reactions think

about what are the specific enzymes that are most notable for this are the atp synthase or atp atp aces i apologize atp synthase is right here this is the formation of energy the atp aces will then break up this energy and use the energy all right so you have a certain amount of demand but if you're constantly over consuming then the supply is much higher than the demand of your cells this is you can look at it like the calorie equation but it this is far more complex than the the calorie equation but we're not

going to go into that not here at least so the point is that supply increases so substantially and because you don't have this drive to to generate more atp you have the supply of energy that's constantly being supplied in nadh and fadh to this electron transport chain the problem here then is that you get what's known as electron slippage or electron slipping which is those energy packets i was talking about that get taken off of nadh so nadh will donate and fadh will donate these electrons or these kind of energy packages and what's normally happens

is they move from one complex of the electron transport chain to the next and as it happens that then energizes the these complexes to then pump these uh protons back out as we explained earlier but if you haven't if you don't have a drive if the atp synthase is kind of moseying about it's just slowly producing energy because there's no demand for it it's supply and demand right that's why i've got supply and demand here then in that situation you have these electrons that don't have a place to go so they will slip or there's

there's pressure for them to slip out of the location that they're supposed to go in because maybe there's another electron there already so as a result these free electrons will sometimes interact with other molecules and generate what are known as reactive oxygen species which as a general term is called oxidative stress these ros molecules and i've discussed this ad nauseam and i'm which pales in comparison to 30 years from now i will have discussed this ad nauseam x infinity but ros molecules well then because they're unstable they need something else they need it's like uh

they're they're they're like addicts they need something else they need another hit of something uh these molecules will then run into other molecules that make up for example these protein complexes or the inner membrane or other aspects of the cell that are you know stable and functioning those molecules will run into those complexes those proteins fats carbs whatever it is that the cell is using for for a particular function and will rip away other electrons and will rip away other components of those complexes now this leads to damage of the cell that's really all that

we need to know that ros if it's over abundant will lead to damage of the cell now one question i got for the last episode as well is that well how do we completely do we completely eliminate is there a way like this fasting for example does that completely eliminate ross no it doesn't and you don't want it to because ros is while it is you could consider it a byproduct of this normal functioning even under normal supply or low supply you're still going to have a little bit of ros production because you need it

your cells actually depend on ros to signal within within themselves so it's not like they're completely a negative thing but they serve a function but if they're over abundant they are extremely negative and in this situation they are extremely negative because your cells your mitochondria have different ways of handling these ros so the healthier you are the healthier the mitochondria that you have the more able they're able to deal with these ros through like the glutathione pathway or some other antioxidant pathway however if you continuously bombard them then eventually that leads to ros just accumulating

so much that it does so much damage to the mitochondria and we'll we'll discuss uh one way that that actually affects your two ways actually that that affects you so this is kind of an overweight situation if you can if a person is continuously over consuming where their supply is continuously happening this is continuously happening i just want to throw in here real quick in the first version of this video that i i produced i i did want to mention that look some people get really anal about well then does that mean that i can

never over consume no it doesn't it's it's almost never the case that you should go to an extreme on anything um i really think that like if you have a week where you're going to the bahamas or you have a week where you're going on vacation or family's coming over it's thanksgiving or whatever it might be do you enjoy yourself this system is is such a like think about it there's two things one think about it within the realm of your entire year or multiple years it's going to have no impact but secondly your bodies

also has robust systems to protect against this especially in the short term so i wouldn't worry about if you over consume for a day or a week the problem is when you over consume continuously over time for months and years of time then yes that's a problem because this is occurring beyond just the fact that a person is likely gaining weight all right so let me jump over now to diabetes let me explain this mechanism here i realize this might look extremely unfamiliar to you but it's really not that complex so right now we're looking

at a beta cell so a beta cell is a cell that is found in your pancreas your pancreas what does it do your pancreas senses the energy state in your bloodstream specifically through glucose it does it through fat as well but it mainly does it through glucose and what it does then is it releases insulin so this is the mechanism by which and i'm going to describe two mechanisms but this is the main mechanism by which insulin is secreted i'll walk you through it so just to just to give you an overall physiological explanation is

that when you eat carbohydrates then your blood sugar increases and then the only way that it decreases back is if you have the release of insulin from these cells right here so you have an increase in blood sugar this that gets sensed because it will enter the beta cells just like it enters every other cell and at this point then you have this chain reaction that leads to the insulin release i'm going to explain to you how not only how the mitochondrion has two different ways i'm going to explain two of them but there's probably

more two different ways of affecting this insulin release and how this could lead to insulin resistance all right so glucose levels increase you have this increase in the blood stream out here it enters through a glute transporter which then this glucose then gets converted through the metabolic pathway glycolysis to pyruvate i'm going to tell you what's important this is not important yet but the point is that glucose enters the beta cell it gets converted to another molecule pyruvate then it enters the tca cycle let me walk you through the tca cycles how we get this

nadh and fadh so the tca cycle converts pyruvate technically gets converted to acetyl coa then gets converted to nadh and fadh which then goes through the respiratory change chain let me go back here this is the respiratory chain right here this is another name for the electron transport chain this then leads to the production of atp as we see here through the atp synthase so the atp levels within the beta cell then increase or the ratio between atp and adp you don't need to know that but the point is that glucose eventually gets converted to

nadh and fadh we get an increase in energy those are the big main points at this point so then this change in energy is sensed by a potassium channel that's found embedded into the cell membrane so we're not talking about the mitochondrial membrane we're talking about the cell membrane now this cell energy as it increases it actually closes the potassium channel so normally potassium would be flowing outwards so potassium is inside the beta cell and it is a positively charged ion so it would flow outwards and if you move a positive to outside of the

cell this makes things more negative in here now because we've closed this the potassium can no longer get out therefore there's a buildup so let me start down here so there's a build up suddenly it closes and it starts building up potassium and the charge inside the cell is more positive as a result this then leads to what's called membrane depolarization which is essentially just an increase in the charge of the the cell and this then leads to the opening of calcium channels that allow calcium into the beta cell so this all gets tripped and

this then leads to insulin being released so insulin is calcium sensitive so insulin is then released i suppose i'll preempt one of the questions that might come from this does this mean that then i need to consume more calcium does this mean i need to consume less calcium no your body is extremely accurate at maintaining a incredibly tight range of calcium that it will modulate based off of a communication between your parathyroid and your kidneys and your bones so should you be consuming calcium of course but should you be consuming astronomical amounts of calcium to

make sure that you're secreting insulin the answer is no so insulin is then released and then insulin will go and bind all the peripheral tissues that i don't have displayed here and then the blood sugar that has elevated right we're up here in this makeshift graft that i'm creating with my mouse and then the blood sugar will then enter the peripheral tissue so the blood levels will then decrease again hopefully that that was well explained honestly that was much better than my first attempt in my first video so there you have it that's how mitochondria

will energy increase the energy which will then have this cascading effect however now i want you to think about one thing then i'm going to introduce the second concept the first thing that i want you to think about is what happens if you constantly have elevated levels of food consumption then you're going to continuously be stimulating this this process to happen constantly releasing insulin now eventually the constant release of insulin means that the peripheral tissues will become insulin resistant because you have this constant binding of insulin to these receptors these insulin receptors on all the

peripheral tissues and we've discussed some of the intracellular mechanisms before so i won't go into those but i certainly can cover those again but in those peripheral cells what happens what that leads to insulin resistance all right so another question that people might have is all right well then if it's glucose that does this is the main driver of this then i should just avoid carbohydrates and that's very rational thought process and to a degree you'd be right but really it's over consumption as a whole because fats can also have peripheral impact on all the

peripheral cells as well so it's not just based on the beta cell and fats do lead to the secretion of insulin just not nearly to the degree that glucose does and if you're scratching your head and you're thinking what how's that possible well i have some content on that as well so you can look up you can look up fat secretes insulin physionics something like that and you'll find a video where i show data explaining and some of the mechanisms for how that happens so no you should not just eliminate carbohydrates and therefore you will

eliminate this whole problem however that said a low-carb diet is i think i would say maybe especially beneficial or especially potent at reducing this insulin insensitivity or insulin resistant effect but the overall point though is over consumption so if you were to suddenly start under consuming and you're still consuming carbohydrates this whole insulin resistance this whole mechanism is normal but this insulin resistance aspect will decrease regardless so i don't want to call it a mood point i think a low carb diet adds an added element of protection but i don't think that you have to

do a low carb diet let me just put it that way okay so that said now so this is all from over consumption you know consumption in general leads to this process but over consumption leads to overproduction of insulin and release all right so now there's a second element here which isn't too different but ultimately you have the exact same things that are happening but not only is insulin triggered to be released through calcium you also have the trigger of insulin release through reactive oxygen species generation and as we discussed here that you have this

over production of ros so what do you think that means well it means that if you're continuously over consuming then you're also not only just going to be working through this mechanism of an energy sensing mechanism but you're going to be going through the secondary mechanism as you're constantly building up ros from the constant over consumption this then leads to more and more insulin so you have a double whammy a double effect here of leading to insulin secretion so this can eventually lead in a very layman's terms to beta cell exhaustion as it continuously has

to produce insulin and release this insulin and therefore then you get beta cell failure so this is a great example of let me switch over to my so you can see me for a second uh unless you regret that in which case sorry um this you can imagine in a in a dangerously high level of diabetes situation that you typically have elevated insulin levels if you're in a later progression of diabetes type 2 you have this elevated insulin level that's partly at least at the very least partly because of these two mechanisms probably majorly because

of these two mechanisms constantly forcing the beta cells to be releasing insulin releasing insulin so a solution as you probably already know at this point is under consume or consume less and then suddenly that pressure on the beta cells is reduced so that they can recover assuming that they can recover okay so now i wanted to touch on one more thing uh actually i was going to touch on two more things i was going to mention the fasting bit after this so in this situation here so in the last video we discussed how the morphology

of the mitochondria changes meaning that the the shape of the mitochondria changes and with nutrient excess you get this fragmentation of mitochondria in a starvation condition as as we discussed there was the elongation of mitochondria which actually protected the mite the longer elongated mitochondria from autophagy which is right here displayed right here i'm not going to go into all the specifics here but you have the lysosome that's integrating with the autophagosome and then it goes through and well actually this is after the fact but then it goes through and destroys all of the damaged or

necessarily damaged mitochondria so in a starvation condition these mitochondria will tend to be a lot longer at least the healthy ones will be a lot longer and this will protect against autophagy even though you're in a starvation situation and as we know a low nutrient situation leads to greater increases in autophagy but that leads to selective autophagy in destroying only the damaged components all right so that out of the way now over nutrition does the exact opposite while it over nutrition does lead to fragmentation of mitochondria making them smaller therefore making them more prone to

autophagy getting rid of them the problem is that over nutrition or over consumption of food in general or just consumption of food reduces autophagy as a whole so therefore even though they're primed to be taken out to be removed these damaged mitochondria these dysfunctional mitochondria are primed to be removed autophagy itself is reduced therefore you do not have the removal of this of these mitochondria so it's kind of a a funny situation in that they're primed ready to go but then autophagy is reduced so they can't they can't be removed so what ultimately ends up

happening is that these dysfunctional mitochondrial then over produce reactive oxygen species you have a more a greater level of ros because this autophagy system can't get rid of them so now you have a double effect you have a doubling effect of of uh ros generation so if you could get rid of these then that would diminish the uh impact on the cell because remember ros will scav will go around and damage components not only of these mitochondria but these mitochondria the healthy ones and will also damage other components of the cell okay so that was

a lot shorter than my explanation the first time first time around admittedly all right so now let's discuss a little bit on fasting and then i'm going to do my concluding remarks um i know that one of the questions that's going to come up or i'll take a a guess at one of the questions that's going to come up because i know you guys really like fasting and so do i i like fasting too as a matter of fact i'm probably start intermittent fasting pretty soon here because i'm getting deeper and deeper into my diet

which is going quite well at the moment but i digress uh with this situation can you fast and get rid of these dysfunctional mitochondria for example because i just said you know starvation conditions that you have increases in autophagy the answer is yes you can so fasting will lead to increases in autophagy and will likely get rid of a lot of these dysfunctional mitochondria however i want you to think again kind of like the scenario i offered with let's say you over consume for a week right you over consume for a week is that going

to have profound negative effects on your mitochondria and your cell health or whatever no right because within the scope of a whole year that's not a huge deal so you should still enjoy yourselves have those vacations have those times when you indulge and have fun and enjoy your life and that will have no or negligible impact on your overall health all right good one second thing this is the opposite will fasting for three days straight or five days straight while that is extreme and you should do it safely will it help will it reverse will

it attack some of these systems the answer is yes but once you stop fasting what do you think happens things just build back up it's it's not it's not like you fast and then you're done like you're healthy now it's you fast and there are some long-term benefits long-term effects that i think scientists are still figuring out i mean i've covered some of those long-term effects and i will be covering more of those long-term effects but you still have to that the most potent thing to do is to fast one and control your weight that's

those two things i would say are primary to avoiding a lot of these things now you can add a bunch of other things maybe some certain supplements like turmeric may have some added benefits as antioxidants and have other benefits beyond that as well that i've covered as well exercise certainly has positive effects you know so but the two main ones in terms of nutrition is controlling your weight so making sure that you're not over consuming continuously and second thing is to try intermittent fasting or if you want to fast every a couple months you know

for a couple days as long as you're doing it safely that will have the most profound effect but this idea that we just fast for five days we just drop some weight because you will drop weight if you just don't eat and then you just go back to your old nutrition lifestyle i'm sorry that's just not going to do it it's it things are you know it's the exact same scenarios i was describing earlier it's just a short time span and then you're just returning back so what impact is that going to have for the

entire year it's going to have pretty small levels i think maybe some greater impact in terms of fasting itself does seem to have some long-standing effects but uh the the effect will be relatively small regardless not that you shouldn't do it uh if you want to but just be aware of that all right so the final thing that i wanted to throw in here is the conclusion so obesity and diabetes are linked in that they both generate significant uh significantly more ros which causes damage to the cells of the body but not only that it

increases the secretion of insulin which in the short term is fine because we have to have it uh otherwise we don't get blood sugar back down or at least through an insulin specific pathway but long term can cause elevated blood insulin and insulin resistance which are major markers of diabetes and because autophagy is inhibited there are more dysfunctional mitochondria that are not cleared away by autophagy leading to a compounding effect of an increased ros generation so there you have it folks i hope that this was informative for you i certainly plan on covering a lot

more on mitochondria and i have some some really cool content coming out in i don't know over the last many months i have some stuff on carbohydrates its impact on weight gain ketogenic diets and their positive effects i have a lot of a lot of stuff so stay tuned for all that and certainly more on mitochondria because my dissertation is related to mitochondria and metabolism so i i'm trying to merge some of my content that i'm re some of the studies i'm reading for my dissertation along with what i'm doing for physionics so hopefully you

don't mind if i if i indulge a little bit because my time is extremely thin at the moment it really has been for a number of years okay well thank you for stopping by i hope you learned something and with that i will hope to speak with you in the future have a great day bye