March 28, 2023

In this video, Dr Mike explains the different stimuli that can trigger the secretion (release) of insulin from the pancreas.

Hi everyone dr. mike here in this video i want to take a look at how insulin is released from the pancreas now remember that insulin is the key that unlocks the doors of the cells to let glucose in from the bloodstream into those cells so the cells can store it or use it for energy so insulin is extremely important now i want you to have a think of a couple of

Things right first thing is we know that insulin is produced by the pancreas so we’ve got this strange structure that sort of sits behind the stomach called the pancreas and there’s a number of little areas on the pancreas which are filled with cells and they’re called pancreatic islet cells now they used to be called islet of langerhans but we stopped naming

Things after old dead guys a long time ago these islets contain different cell types they’ve got beta cell types which produce the insulin and they’ve got the alpha cell types that produce another hormone called glucagon now think of the gone in glucagon this gets released when glucose is gone right there’s not enough glucose in the bloodstream let’s release

This to increase blood glucose insulin drops blood glucose glucagon increases it and the pancreas specifically these islets are the area that’s most responsible for these hormones to be produced now these hormones are released into the bloodstream to have their effects on a wider array of tissues of the body i want to look at how insulin specifically is released

From the pancreas now i said they came from beta cells so i want to draw up a beta cell here and the first thing i want to talk about is the fact that the major stimulus for insulin to be released is glucose so if i draw glucose up like that glucose once ingested so let’s just say you have a meal you have a meal that goes through your digestive tract gets broken

Down the complex carbohydrates turn into basic glucose which gets absorbed through your gut wall into the bloodstream now what when it’s in the bloodstream it travels all throughout the body and it goes to all the tissues of the body including the pancreas which means the concentration of glucose is high in the blood compared to the concentration of glucose in

Tissues so that means you’ve got a high content glucose outside the cell compared to inside and we know what happens in these scenarios diffusion high concentrations always go down to low concentrations but in order for this glucose to get in to this beta cell it needs a transport mechanism and this transport mechanism takes that glucose and throws it inside and

What this is called is a glucose transporter and there’s a couple of different types this glucose transporter is called glut glue standing for glucose t4 transporter so glut 2 that’s the specific type it’s actually reversible i can throw it in and throw it out now takes this glucose in down its concentration gradient now glucose is inside the cell we all know that

Glucose undergoes a number of different reactions it will turn from glucose into glucose 6-phosphate and you know that now this is starting the glycolysis pathway to produce atp that’s where we’re going here and not for this to happen we need an enzyme called glucose kinase i’m saying this because glucose carney’s is one of the rate limiting steps in this process

So glucose 6-phosphate going through the glycolysis pathway well ultimately turn into something called pyruvate pyruvate jumps into the mitochondria and we know a couple of things happen in the mitochondria that pyruvate undergoes the krebs cycle it also jumps into the membrane of the mitochondria undergoing oxidation and what it ends up spitting out at the end

Of the day is a whole bunch of atp and atp is produced from adp adenosine diphosphate two phosphates add an additional phosphate atp triphosphate this is the energy currency of the body we need this well now what does this got to do with insulin release all right we’re getting there a couple things let’s draw up two channels of great importance there’s a channel

Here and channel here this channel what it does is it’s a potassium channel we know that we have high concentrations of potassium inside ourselves compared to outside and that means potassium wants to go outside what this channel does is it has a on it and this lid is open when there’s no glucose inside the cell so think about it like this let’s say that there’s no

Glucose so this process doesn’t happen if this process doesn’t happen atp is a produced and so we have high amounts of adp because it hasn’t yet been turned into atp so high adp and low atp and what this means is the adp sits on the lid of that channel keeping it open that’s adp now if it keeps it open it means potassium can leak out of the cell and if potassium

Leaks out the cell it takes it’s positive charge with it so all this positive stuff leaves the cell and that means the inside of the cell becomes a little negative compared to outside so the inside becomes negative compared to the outside because all that positive potassium is leaving the cell now if you were to compare the charge difference from inside to outside

You’ll find it’s going to be around about negative sorry negative 70 millivolts let’s just quickly draw this up in a chart right on a graph let’s say we’ve got negative 70 here we’ve got negative 50 here we’ve got zero here let’s say we’ve got positive 30 here right now we’re at negative 70 okay so this is what’s happening when we have glucose glucose turns into

Pyruvate jumps into the mitochondria produces atp from adp so when glucose is in the beta cell adp levels go down atp levels go up that adp jumps off the lid the lid closes now which means potassium doesn’t leak out the cell and the potassium remains inside the cell and the increased amounts of atp atp actually sits on this lid and keeps it shut this is called

An atp sensitive potassium channel atp sensitive potassium channel yeah if this potassium stays inside it’s no longer negative if it’s starting to be a little be more positive which means this negative 70 drifts up into it being a little bit more positive if it becomes so positive that it hits negative 50 well this is when this other channel kicks into play this

Channel is sensitive to charge so what will happen is once we hit negative 50 millivolts which is now what’s happened we’ve now gone to negative 50 millivolts this channel opens its lid and it’s a calcium channel and we know calcium sits outside the cell all right that means calcium wants to come in and when calcium enters a cell like this calcium as we know when

We did the nervous system likes to push the vesicles that contain substances out inside the beta cell we’ve got these little vesicles that hold insulin calcium says alright time to go and this vesicle merges with this membrane and pushes the insulin out insulin release is mediated by calcium influx into the beta cell all right let’s just quickly reiterate glucose

Needs to get into a beta cell glucose needs to turn to pyruvate via khou kinase pyruvate needs to get into the mitochondria undergo the krebs cycle and oxidation to produce atp atp shuts the atp sensitive potassium channel and potassium increases inside making it more positive this positive change is called depolarization this event is called depolarization the

Cell needs to depolarize in order for calcium channels to open for calcium to enter and calcium pushes insulin out reason why i’m telling you all this is because if you want to regulate insulin from being released or not being released you either need to play around with whether there’s going to be glucose in the cell where the glucokinase is working properly

Whether you have enough atp where the calcium is coming in or whether you’re depolarizing the cell you can actually do any of these particular things really and it’s going to promote or inhibit insulin from being released so for example there is a genetic disease which is glucokinase mutation this gene has a mutation so this enzyme is dysfunctional which means

Glucose doesn’t turn glucose-6-phosphate none of this happens insulin isn’t released if insulin isn’t released the glucose remains high in the blood if this happens over time that’s diabetes so a mutation in glucokinase can form or cause a relatively rare form of diabetes called no d modi is maturity onset diabetes in the young due to a mutation and glucokinase

But what if you want to promote insulin being released that’s stopping it right and that’s by nobody’s fault but a mutation there are certain drugs for diabetics because in diabetes you want to release the insulin at specific times right so there’s drugs called oral hypoglycemic drugs it drops blood glucose levels that’s the plan if glucose stays high in the blood

It damages blood vessels damages tissues it’s bad news you don’t want high glucose in the blood for a long time so what can we do to promote that release well this is what these oral hypoglycemics do they block this potassium channel pretty much the same way atp does these drugs are called sulfonyl ureas okay and they still follow your ears sit on that channel lid

Stopping potassium potassium stays inside depolarizing the membrane opening calcium channel calcium forces insulin out so there’s so follow your ears that’s their mechanism of action now there’s things in the body that also do this so for example it’s not just glucose glucose isn’t the only nutrient that does this amino acids do this fatty acids do this ketones do

This these are all nutrients all of these nutrients can jump in and promote insulin release but has this they maybe are do it by themselves but if they’ve got glucose with them it’s potentiated it’s supported its enhanced it’s a synergistic relationship there’s more than the sum of their parts so if amino acids are in the beta cell with glucose way more insulin

Is released than just amino acids and just glucose by themselves right the thing is the way they work is they basically when they come in amino acids and fatty acids pretty much jump in at this phase right so that means and ketones basically jump in to around about this face because ketones are pretty much just a bunch of acetyl co ways snap together and acetyl

Coas is a substrate in the krebs cycle so they all jump in which means the way that they the way that amino acids fatty acids and ketones promote insulin release is simply by producing atp but in addition to that there’s certain amino acids like arginine and arginine is a positively charged amino acid there’s other positively charged amino acids the cationic and

If they have a positive charge it means they’re going to depolarize the cell similar to keeping potassium in and that means that these amino acids probably have a greater effect in pushing insulin out then other amino acids alright okay so there’s actually another way amino acids can jump in by piggybacking with sodium which has a positive charge and sodium will

Do the same thing positive charge depolarizing the cell calcium insulin out but there’s other things in the body okay so think about the sympathetic parasympathetic nervous system they play an important role because what they do is so the parasympathetic nervous system is the rest and digest right and the rest and digest system is going to function predominantly

Through that vagus nerve down this area the vagus nerve is the tenth cranial nerve it releases acetylcholine and acetylcholine promotes insulin from being released but makes sense resting and digesting you want insulin to be released with the sympathetic nervous system which is the fight and flight it’s a little bit more difficult because when we have a look at the

Sympathetic nervous system what we’re going to get is this right sympathetic nervous system here’s the brain here’s the brainstem cerebellum the thoracic and lumbar area is the area in which neurons exit for the sympathetic nervous system sympathetic nervous system fight-or-flight now the preganglionic neurons there’s one that one group that to the kidneys the prey

There’s usually two neurons this is the first one and it goes to the kidney and goes to the adrenal gland on the kidney and it stimulates the adrenal gland to release two things of importance cortisol and adrenaline now they’re both hormones what cortisol does is it increases blood glucose levels because it tells stored glucose in the form of glycogen to be released

Blood glucose levels go up if blood glucose levels go up glucose comes in again so it’s released adrenaline what adrenaline can do is similarly increased blood glucose levels but adrenaline can directly bind to b2 to receptors on this process and promote insulin release as well you don’t want this happening over time you don’t want increased cortisol levels over time

Because it can result in diabetes because increased blood glucose levels over time are going to exhaust this cell anytime you exhaust the beta cell overly pushing out all this insulin it gets tired and stops that’s type 2 diabetes so you’ve got these systems working as well there’s other systems right so there’s what’s called the incretins and there are a whole bunch

Of digestive hormones that get released and they pretty much all push out insulin right gip glp-1 for example cholecystokinin they all promote insulin from being released one strong negative mediator here is somatostatin somatostatin likes to stop everything basically in the body and somatostatin will stop insulin release so there’s a run-through of insulin released from the pancreas

Transcribed from video
Insulin Secretion By Dr Matt \u0026 Dr Mike