Endocrinology | Pancreas: Glucagon Function

all right Niners in this video we're going to talk about the pancreas but specifically we're going to focus on the activity of glucagon okay so if you remember if you guys watched our video on insulin you know go back if you guys haven't watch that video on insulin get caught up on what was happening with the pancreas because we're just going to go ahead and Dive Right In but just as a quick quick quick review remember the pancreas is a heterocrine gland right and so that means means that it's actually made up of two components we told you right that one was the exocrine which was the asini that was the one that was accounting for about 99% of the pancreas it was the one that was making the pancreatic juice and which was rich in digestive enzymes and bicarbonate the other part was the eyelets of langeron okay so these are the two parts of the pancreas these are the two components and if you remember we divided the eyelets of langerhan into two cells the alpha cells and the beta cells right those are the two components now if you remember we said that the beta cells that was the discussion for the insulin they were the ones that were responsible for secreting insulin and if you remember insulin was stimulated by hyperglycemia hyper glycemia right so it's anything greater than about 120 uh maybe even tops 130 milligrams per DL whereas the alpha cells they're the ones that are secreting glucagon and glucagon it's primarily stimulus is actually going to be hypoglycemia and again you can remember that by that little thing I told you that it's released whenever glucose is gone whenever it's low and generally anything below 70 maybe even a little bit below that milligrams per DL so if you remember what was that range the normal range is about we like to give it about 80 to 120 that's like your general range okay for every average individual now like I said anything below 80 and maybe even a little bit below 70 right is a primary stimulus and it's hypoglycemia right so that would stimulate these alpha cells to secrete glucagon and again how do you remember alpha cells make glucagon because there's an A in glucagon and an A in Alpha okay there's no a in insulin then if you remember anything greater than 120 maybe even a little bit even 130 is hypoglycemia and that's a stimulus for insulin we're going to talk about primarily what then what's the stimulus of glucagon it's when glucose is gone so it's hypoglycemia right there's low glucose levels so if there's low blood glucose levels hypoglycemia what is that mean that means that very little glucose is going to be coming into this actual Alpha cell okay so it's transporting this glucose into the alpha cell now the certain literatures will say that this actual transporter it's not glut 4 it's technically glut one okay whether or not that's significant it's not really important in this conversation I'm just giving you a comparison as to what it was insulin right insulin specifically in the pancreatic beta cells had those glut two receptors so let's say that it's glut one specifically on the alpha cells but neither here nor there not too important that glucose though if you remember gets converted into pyruvate right and if you remember pyruvate gets taken into the mitochondria and converted into acetal COA that under go a lot of that crab cycle activity then it gets taken to the electron transport chain those nadhs and fadh2s and produces ATP but if there's very little glucose getting into the cell you're not going to really make a lot of ATP but here's where it's a little funky you see these channels here on the membrane these channels right there they're sensitive to that ATP so whenever there's actually ATP when there's very little amounts of ATP these channels are really sensitive to charge so we don't really they're not really going to respond to a lot of like charged particles or whenever it's really really when there's a lot of glucose coming in inside of the cell there's a lot of potassium that accumulated if you remember in this case it's a little different when ATP binds here where there's very little ATP these channels are very very sensitive they still actually close they still close and potassium ions are still going to be blocked from exiting but it's not going to be so many potassium ions accumulating in this area that it's so large that it causes a significant membrane depolarization there's going to be less membrane depolarization if there's less membrane depolarization this calcium channel is going to be more sensitive to that and it's going to open up and allow for calciums to start moving into this vicinity so let me explain this one more time very little glucose makes very little pyruvate which makes very little acoa which makes very little ATP now this decreased amount of ATP due to decreased glucose levels these pottassium channels are very sensitive to ATP but you don't want to produce too much ATP because if it's too much ACP it's going to affect these channels another thing is That these channels are really really sensitive to charge if the inside of the membrane becomes too positive these membrane channels become really really weird okay so you don't want there to be too much of a membrane depolarization so when ATP binds it still closes those pottassium channels and potassium accumulates but it doesn't cause as much of a significant membrane depolarization and then these calcium channels due to that not a significant amount of a membrane depolarization opens and calcium Flows In why am I saying this because guess what if if your glucose levels are really really high you make too much pyruvate you make too much acetylcoa you make too much ATP too much ATP is going to bind onto this and keep it closed very very strong and tightly so then a lot of potassium is going to stay into this cell and what's going to happen to the cell it's going to become extremely positive remember what I told you when it's really really positive inside of the cell guess what it does to that calcium channel it closes it and calcium can't come in I'm going to explain why that's important but again remember we're talking about low glucose levels low ATP less sensitive effect on the potassium channels potassiums do accumulate but it's less of a significant effect of membrane depolarization which causes these voltage sensitive calcium channels to open and the calcium Flows In in the meantime remember these actual pancreatic alpha cells are synthesizing this glucagon so it's going to be like pre-synthesized now there is other stimuli that can affect glucagon synthesis and secretion besides this actual low glucose one one of them is they believe neuro epinephrine or epinephrine can actually so your sympathetic nervous system so SNS sympathetic nervous system they believe that this can be a stimulator of specifically glucagon secretion okay that's one mechanism they also say that it could be sensitive to kicy ainin which is a hormone produced by your intestine and secretin which is another hormone produced by your intestine they say that they're also stimuli neither here nor there though just to let you guys know there are other stimulators of glucagon production rather than just low glucose levels but this is the primary stimulus okay so now if you remember let's say that this is a specific Gene and that Gene is getting transcribed to make mRNA that mRNA then goes and it actually goes to these ribosomes that are on the rough endoplasmic reticulum right so it goes out to this area and then if you remember what is it going to do it's going to synthesize this peptide right and this peptide is going to get pushed into the rough endoplasmic reticulum if it gets pushed into the rough endoplasmic reticulum it's actually forming proglucagon it'll get cleaved and modified and then it'll come out in this little vesicle from the rough ER and then you're going to have in this little vesicle you're going to have that glucagon hormone right then that glucagon is actually going to go to the G G and in the g under goes a little bit more modification reactions and then what happens is it under go specific types of packaging and then look what happens to it out of the goldi Look what comes out of the goldi that nice little vesicle and that vesicle contains glucagon so you could have multiple vesicles out here I could have look I'm going to draw three vesicles just for the sake of it so now what do I have out here I have vesicles containing the glucagon hormone what did I tell you if there's less potassium that's actually getting staying inside the cell there's less of a significant me membrane depolarization and it's just the right amount of membrane depolarization in other words becoming more positive in the cell that caus these calcium channels to be very sensitive and open when the calcium comes in what happens remember there's proteins here on this membrane and there's proteins here on that vesicle what calcium does is he links these together he helps them to migrate and fuse with that when this vesicle fuses with that cell membrane look what happens it fuses and opens up into the extracellular environment if it opens up into the extracellular environment what is it going to do it's going to release out what glucagon and glucagon gets pushed into the bloodstream and we just synthesize glucagon okay now again why am I telling you that this whole thing with the at P because if your blood glucose levels are really really high you're going to make too much pyruvate too much pyruvate makes too much ATP too much ATP causes these pottassium channels to become even really really sensitive and accumulates too much potassium inside of the cell when there's too much potassium accumulating inside of the cell it causes the cell to become extremely positively charged and when there's an extreme positive charge that inhibits this calcium channel calcium can't come in if calcium can't come in can you actually for these vesicles to migrate and release glucagon no so that's why low glucose is a stimulator but high glucose is an inhibitor of glucon secretion and again remember that cck stands for chys theine secretin which are gastrointestinal hormones norepinephrine epinephrine are also stimuli of glucagon secretion okay so now we made our glucagon and again let's recap what was the glucose levels in the blood they were really really low now Prim primarily when are your glucose levels low okay besides having like a pancreatic insulinoma you're generally going to have low glucose levels in a condition which is called the fasting State okay so your fasting State meaning that your postabsorptive state so in other words you haven't eaten in a while okay so you haven't eaten in a while this is generally the time whenever your glucose levels are low physiologically you know not assuming any type of pathological conditions if your glucose levels are low in the blood that's not good because your brain depends on glucose and so do do other tissues so we want to be able to get the glucose in the blood up how do we do that let's see what glucagon does first thing glucagon does it comes over here to the liver it loves to act on the liver so let's say here's this glucagon represented by that black dot here's our glucagon okay and he's ready to help what does he do he binds onto this G protein coupled receptor and you guys should know this mechanism by freaking memory now it stimulates a g stimulatory protein G stimulatory protein is normally bound to GDP which keeps it off but then when it's bound to GTP it's turned on goes and activates a affector enzyme this affector enzyme is actually called a denate cyclas and then a denate cyclas takes ATP and converts it into cyclic and en cyclic a activates protein cyas a okay why is all of this important cuz you remember GL glucagon is a peptide hormone you can't pass through the cell to exert its effects it's got to make second messengers so how does he do this now if you remember during the actual fed State we had a specific molecule that we actually synthesized if you guys remember it was called glycogen so glycogen is just a polymer of glucose right so this is our glycogen molecule so let's call this again this is called glycogen the first thing that this glucagon is going to do is is it's actually going to help to convert this glycogen specifically into the basic building blocks of glycogen you know what the basic building blocks of glycogen is it's called glucose what is it doing how is it working the other specific enzymes we'll talk about this in Biochemistry there's a specific enzyme called glycogen phosphor but protein kinas a is stimulating that enzyme and causing it to break down glycogen into glucose why is that significant because where can that glucose then go look where it goes into the blood if it goes into the blood what happens to the glucose level so now these glucose if you're bringing a lot of glucose into the bloodstream from that glycogenolysis which we're going to name what's going to happen to the glucose levels it's going to increase so again what is this reaction here that just occurred this reaction here is called glyco genalysis gnarly that's pretty cool right now what else can happen gon's also pretty cool because not only does he promote glycogen alysis you know he uses other molecules so before we keep going let's show what he does on the adapost tissue because it's going to be related okay so Glon comes out here and what he does is he acts on this receptor this is adapost tissue so this is your fat tissue right so again who is this guy right here this is your glucagon he's again he's excited and ready to help what is this glucagon let's actually make him a little bit happier you know he looks like a little angry all right so glucagon what is he going to do he's going to activate this receptor this G protein coupled receptor so again G stimulatory binds to GTP which activates him and turns him on when that happens he goes and activates an affector enzyme if you remember that affector enzyme is actually called ad denate cyclace when it stimulates and activates a denate cyclas denate Cycles takes ATP and converts it into cyclic and then cyclic activates protein kinase a again why is this important because glucagon can't just get into the cell and start exerting its functions it has to do with your second messenger now why is that important you guys have probably seen this a thousand times already look what I got here you see that enzyme right there this enzyme look at him he's ready to roll okay this this enzyme is ready to roll this enzyme is called hormone sensitive lipase guess what protein KY does he comes over here and he'll phosphorate that enzyme activating the enzyme you know what that hormone sensitive lipase is going to do it's going to start cutting those specifically those Ester bonds that c the triglycerides together and then when it breaks that up it's going to break it into its two constituents what are the two constituents of this triglyceride so this triac glycerol triglyceride tag right it's just another word for saying triglyceride or trial glycerol it's going to break it into its two components one is glycerol the other is these fatty acids okay so the other is fatty acids so these are the two components that are going to be broken into so this glycerol is really really critical let's bring this glycerol over here now and it's going to come into this liver cell now what happens with this glycerol is that protein kisee a he's going to work through special types of mechanism looks look what he does he comes over here okay and he acts on there the specific enzymes and there's specific enzymes that help to be able to convert that glycerol into glucose specific enzymes so you can take the glycerol turning into dhap and then shift it upwards to make glucose you know what else it can do you know there's other different types of molecules that are present inside of the liver that are really really important a lot of other different types of molecules this one we can say are called Amino acids okay so you can have amino acids in the area or you can have glycerol in this area look what that protein kyes a also does he also says okay I'm not only going to stimulate that pathway but I'm going to come over here and I'm going to stimulate this conversion of amino acids into glucose and it also stimulates this it under goes transamination and then after that it gets turned into maybe a specific keto acid or into pyu and then gets converted into glucose so again let's look and see what this guy's doing on the liver one he's activating protein Kye a what is protein KY a doing activating glycogenolysis breaking down the glycogen into glucose by stimulating glycogen phosphor right it's also taking the glycerol which was coming from the adapost tissue and then stimulating the pathways to convert him into glucose and it was also stimulating certain amino acids to undergo transamination and they get converted into glucose also there is an exception here if there's fatty acids that are odd chain so odd chain fatty acids just for those of you students who maybe want to know a little extra these odd chain fatty acids can also get converted into glucose okay what is that called whenever you're taking glycerol amino acids and even lactic acid and even odd chain fatty acids and turning them into glucose that is called gluco neo genesis okay gluco neo genesis so two really important effects here one was glycogenolysis one was gluconeogenesis and what is this called when you're breaking down triglycerides into glycerol and fatty acids via the hormone sensitive lipace this is called specifically this event here it's called lipolysis okay so now one last thing here gugan also recently has been found to have an effect on the heart specifically The myocardium of the heart so let's say here's our glucagon and here's you know glucagon and again he's got he's he's excited he's ready ready to be able to help he wants to be able to do whatever he can to get those glucose levels up he also has another effect that is independent of the glucose levels he actually does something really cool I just thought I'd mention it he can activate that g stimulatory protein again right which again goes and activates a denate cyclace which then actually does what takes ATP and converts it into cyclic and then cyclic a activates protein kise a what's that significant for protein kinda comes over here and activates and opens up specific channels these specialized channels these specialized channels are for calcium and calcium starts flowing in to this muscle cell why is that important because if you get a lot of calcium into that muscle cell what's it going to be useful for it's useful for that crossbridge formation for the contractions right to bind on troponin change the shape of the tropomyosin allow for the the actual myosin to bind into actin and then cause the sliding of those myofilaments if there's more calcium than usual won't there be enhanced contractility yes so what's the effect that glucagon can have on the heart he can increase contractility what does that call when a certain agent can increase contractility it's called a positive IO Tropic agent okay so if he increases your contractility you can technically increase your stroke volume your cardic output maybe even your BP but to come back to this if you actually have glycogenolysis right that's going to get glucose into the blood if you have glycerol amino acids lactic acids odd chain fatty acids getting converted into glucose via gluconeogenesis and that glucose that you form gets into the blood what happens to the glucose levels you're going to bring those glucose levels up because you're accumulating a lot of glucose and you're going to bring those glucose levels up to where you can get it right within that range again of about 80 to 120 mg per DL that would be the desire because then once you start getting it too high what will happen if it gets too high you guys remember if it starts to get too high what happens if you get a lot of glucose it makes too much pyruvate a lot of pyruvate will make too much ATP too much ATP will affect these potassium sensitive channels to the ATP if too much ATP it'll cause a significant membrane depolarization and if it's too membrane depolarized it inhibits the calcium channel and then not as not no calcium comes in if calcium doesn't come in can you cause the release of glucagon no and then glucagon doesn't get released who does get released if it's too high insulin and it's a beautiful way of having this Effect called antagonism antagonism is when two hormones are opposing each other so glucagon wants to be able to do what to your glucose levels bring it up insin wants to do what to your glucose levels bring it it down there's also synergism if you could think about synergism it would be other hormones that are performing the same function so for example glucagon has almost the exact same functions as epinephrine so those two are synergistic to one another they love to be able to increase the blood glucose levels and there's one last term called permissiveness which is when one hormone needs to be present in order for another hormone to function okay and that could be a perfect example of thyroid hormone thyroid hormone is really necessary in order for certain types of steroid sex hormones to cause brain development okay but I just thought I'd throw that at you again all right nine in this video we talked about a lot of information I really hope you enjoyed it I hope it made sense if you did like it hit that like button put a comment down in the comment section subscribe we really want to hear from you guys all right nine nerds until next time

Channel: Ninja Nerd

Views: 321,015

Keywords: pancreas, glucagon function, glucagon, glycogenolysis

Id: b2Kcp5hJBXE

Length: 23min 45sec (1425 seconds)

Published: Thu May 11 2017