Lecture 4- . The Endocrine Pancreas Flashcards
Learning Outcomes
*Distinguish between the endocrine and exocrine roles of the pancreas
*Describe the morphology of the endocrine pancreas
*Explain the pancreatic regulation of glycaemic
–Insulin & diabetes mellitus
–Glucagon
*Be aware of other pancreatic hormones
–Somatostatin
Exocrine vs Endocrine Pancreas
So before we get onto the endocrine pancreas,
I just want to remind you about the difference between endocrine and exocrine secretion and described to you very briefly,
because you’ll have much more detail about this in the GI tract physiology lectures.
So exocrine secretion is secretion via some kind of specialised duct.
So a tube leading from um a region of tissue onto an epithelial surface.
So for example, your salivary glands produce saliva secretions through a tube on the epithelial service in this case is the inside of your mouth.
Um, the sweat glands. Sweat is a form of exocrine secretion.
There are ducts leading from the sweat glands onto the epithelial surface, which in this case is your skin.
And the pancreas also has an important exocrine role because it secretes, digestive juices and liquid that’s rich in bicarbonate onto its relevant epithelial surface, which in this case is the duodenum.
And the exocrine secretions from the pancreas mix with the stomach contents.
As soon as they’ve left the stomach in the duodenum, the bi carbonate neutralises that stomach acid and some of the enzymes within
that pancreatic exocrine secretion start the process of GI tract digestion.
So that is very simply the exocrine form of the pancreas.
But remember the endocrine secretion is very, very different.
Endocrine secretion does not involve a duct.
It’s ductless secretion. And it’s not released directly onto an epithelial surface.
It’s released into the blood. So there’s a fundamental difference between exocrine and endocrine secretion.
*Exocrine activity = secretion via a specialised duct → epithelial surface
–e.g. pancreas, salivary gland, sweat gland
*Exocine pancreas aids digestion via secretion to the duodenum
–Contains bicarbonate & rich in digestive/lytic enzymes
–85% of pancreatic volume is associated with exocrine function
*Remember: endocrine activity = secretion directly into the blood without a duct
Morphology of the Endocrine Pancreas
And on the right of this slide is another very simplistic PowerPoint cartoon that I’ve drawn for you.
Uh, the green represents a cross-section through the pancreas, and you can see these little black dots found throughout.
And these are called the Islets of Langerhans. And they only make up about 2% of the mass of the pancreatic tissue.
But despite being very small, they are incredibly important.
And it’s the islets of Langerhans that is the endocrine part of the pancreatic tissue.
And as we’ve seen with all the other endocrine tissues that we’ve looked out so far, they’re highly vascular.
And this makes sense, of course, because they’re producing hormone secreted into the blood.
So it makes intuitive sense. They must have a really good rich blood capillary network.
They’re also innervated by the autonomic nervous system.
And as we’ll see in a few slides time the autonomic nervous system kind of regulates the endocrine output from these bits of tissue.
And within the islets Langerhans there are three main endocrine cell types alpha, beta and delta.
the alpha cells produce a hormone called glucagon.
The beta cells produce insulin, and the delta cells produce somatostatin.
And if you look, um, down the microscope at the morphology of these cells, you will find that they have, a well-developed rough endoplasmic reticulum.
So, RER here stands for rough endoplasmic reticulum and Golgi apparatus.
And the cytoplasm contains, a number of secretory granules.
And that should immediately give you a clue as to what type of hormone we’re looking at here.
And we’re looking at peptide hormones. So of course they need the endoplasmic reticulum and Golgi in terms of their synthesis.
The fact that they’re peptides means that they’re stored in granules products released by exocytosis.
So if you’ve got the weak one content firmly in your mind, that should be quite apparent to you very quickly.
*Small clumps of pancreatic endocrine tissue = islets of Langerhans
–Approx 2% of pancreas mass
–Highly vascular
–Innervated by the autonomic nervous system (ANS)
*Islets of Langerhans: major endocrine cells
–alpha glucagon
–beta insulin
–delta somatostatin
*Endocrine cells are morphologically distinct from exocrine pancreas
–RER/Golgi complex
–Secretory granules (differ for each cell type)
Insulin: Structure and Synthesis
So what is the endocrine part of the pancreas?
Well, if you look at the morphology, the structure of the pancreatic tissue, you find that there are little clumps of cells spread throughout it
So we’re going to start off by looking at insulin, because this is arguably the most important of these pancreatic hormones.
And it’s the one which is most relevant to many people.
We’re going to start off by looking at the very simplistic biochemical structure and synthesis of the hormone,
before we then go on to look at its function.
So insulin is a polypeptide that’s made up of two chains an A chain, and a B chain that are linked by disulphide bonds.
And you can see in the middle here on the right hand side of the slide.
this is a very simplistic cartoon representation of insulin.
These two thick blue lines represent the A, B chains, and the s-s represents that of the disulphide bridges,
two of which link the two chains together, one of which links two different regions of the A chain.
And when insulin is first synthesised, it’s synthesised as a pro hormone called pro insulin.
And you can see that at the top right of this slide here.
So you’ve got insulin, but you’ve also got another peptide that’s bound to that insulin molecule.
And as the insulin is packaged into the Golgi apparatus you get um maturation of the insulin peptide and then in the Golgi apparatus.
This pro insulin is then cleaved into what we call early granules with zinc ions and protease enzymes.
And as it goes through the maturation process, the protease enzyme um digests the pro insulin into two components insulin and C peptides.
And this insulin C peptide. They then stored together in what we refer to as being a mature granule, which contains the fully formed,
biologically active insulin that’s ready to be released by exocytosis.
So there’s a little bit of extra information there that follows on from the OnDemand lecture from week one.
Here we have an example of a hormone that’s first synthesised as a pro hormone,
but then needs to go through a maturation process to actually cause the release of the final bioactive form of that particular molecule.
*Polypeptide (b cells)
–2 chains (“A” and “B”)
–Proinsulin = precursor
–C-peptide = 2ry component of proinsulin
–Importance of post-translational modification
*In Golgi apparatus, proinsulin packaged into “early granules” with Zn2+ & protease
*Cleaved insulin binds with Zn2+to form dense, crystalline core of “mature granule”; C-peptide surrounds core in clear space
*Granule contents secreted via exocytosis
Insulin: Physiological Effects
Most important for a physiology module is, well, what are the physiological effects of insulin?
Well, the first thing to say it’s an anabolic hormone. And to remind you what anabolism is so metabolism, you will know about.
And it has two simplistic forms. We have catabolism, which is the breaking down of large complex molecules into smaller, simpler molecules.
And we have anabolism, which is the building up of large complex molecules from smaller constituent building blocks.
So insulin you can, describes being an anabolic hormone,
because one of its main overall functions is to cause stimulation of production of storage molecules such as glycogen,
lipids and also proteins, and insulin acts by binding to plasma membrane receptors.
Again, if you’re on top of the week long contents and you know the instance of peptide hormone, that should be something that’s not new to you at all.
It binds to these plasma membrane receptors.
And for those of you interested in pharmacology and cell signalling, this is part of the receptor family linked to an enzyme called tyrosine kinase.
So when insulin binds to its binding pocket on the extracellular part of the receptor,
it causes activation of this enzyme tyrosine kinase that’s linked to the intracellular part of the receptor.
The enzyme is activated and then very quickly causes a range of cascades of intracellular biochemical events.
So what is the physiological relevance of insulin binding to its receptor?
Well,
possibly the most important and best studied of these effects is it causes an increased uptake of glucose from the blood into particular tissues.
And we’ll look at these three tissues skeletal muscle, liver and white fat tissue in a bit more detail later on.
Just as in fact, we’ve looked at them in the earlier lecture this week,
but it also causes the cellular uptake of amino acids in the skeletal muscle and in the skeletal muscle,
the glucose and amino acids that have been taken up are then anabolically converted into glycogen and protein,
respectively, and in the liver the glucose that’s taken up is converted into glycogen and triglycerides.
So glycogen fat. And in the white adipose tissue the glucose is then converted to triglycerides after it’s been taken up.
So it’s a taking up of glucose as we know acids into these three tissues.
And then an anabolic conversion of these molecules into larger storage forms.
So that’s an overview of what insulin does.
*An anabolic hormone (stimulates production of glycogen, lipid & protein)
*Binds to plasma membrane receptor (linked to tyrosine kinase)
*↑ cellular uptake of glucose–Stimulates insulin-dependent glucose transporter protein (GLUT4)
*↑ cellular uptake of amino acids
*Muscle
–Glucose → glycogen
–Amino acids → protein
*Liver
–Glucose → glycogen & triglycerides
*Adipose
–Glucose → triglycerides
Insulin: Regulation of Secretion
The next important question is well how is insulin regulated.
Well, given the insulin’s main physiological effect is to cause the uptake of glucose from the blood.
It perhaps comes as no surprise that the main physiological regulator of insulin secretion is blood glucose concentration itself.
And in a hyperglycemic state. So where we have an increase, a rise in blood glucose, for example, after a meal in a postprandial state,
this rise in plasma glucose concentration is a very powerful stimulator of insulin release from the beta cells of the islets of Langerhans.
Conversely, if we have a hypoglycemic state, so a drop in blood glucose concentration that inhibits insulin.
Remember at the level of skeletal muscle, insulin also causes the uptake of amino acid from the blood.
and therefore it might hopefully not be a surprise to you that the concentration of amino acids and also,
to some extent fatty acids in the blood can, stimulates insulin release as well.
But there are other different physiological mechanisms which can also impact regulation of insulin.
One of these is a family of hormones called the incretin hormones.
I mentioned to you right from the start of week one that the gut,
as well as being obviously a key site for digestion and absorption of nutrients, is also an endocrine tissue.
And there are endocrine cells throughout the whole length of the gut.
And some of these endocrine cells produce hormones called incretins.
And these ingredients have various functions. One of the most important roles of these increases is to cause a stimulation of insulin secretion.
And what we think’s going on there is that when the gut senses that there is, um, food passing through it,
what it does is it causes release of these incretin hormones and that, if you like,
primes the insulin secrete response so that as soon as nutrients, particularly glucose,
are absorbed through the intestine, the insulin is already there, primed, ready for a rapid onset of secretion.
So it can deal with that uptake and absorption of sugar from that meal.
So it’s a way of increasing the speed and effectiveness of the response of insulin to a meal that you’ve had.
The autonomic nervous system is also a powerful regulator of insulin secretion.
So the parasympathetic remember this is the so-called rest and digest arm of the autonomic nervous system.
This will stimulate the production of insulin.
Whereas the sympathetic including adrenaline that we talked about the other day inhibits insulin production.
And how can you remember that? Well, remember the sympathetic the bit that controls the fight or flight in a stereotypical fight or flight situation?
You need to be physically active. And so for that yes, you need increase in respiration rates, increase in heart rate,
but you also need an increase in blood sugar concentration so that your skeletal
muscle has a ready source of fuel to cause that physical activity to occur.
Insulin causes a decrease of plasma glucose concentration.
So by inhibiting the secretion of insulin as part of its action,
that is one way in which the sympathetic nervous system enables that rise of plasma glucose to enable the energy availability for the muscle.
So if you think about it using the integrative understanding of physiology, it actually makes perfect sense.
What the autonomic nervous system does, what it does here. Um and finally stress.
Now stress. We’ve talked about a little bit before in the adrenal lecture.
And it can be psychological stress, but it also can be physiological stress.
And in a situation of stress, again, not too dissimilar from the so-called fight or flight response,
typically you want to have increased energy to deal with the stressful situation.
And so stress is another factor that will inhibit insulin secretion as part of a wave rising to blood glucose concentration.
So insulin is regulated by a lot of different things.
But if you use your understanding, your overall understanding of physiology,
it all makes perfect sense how these things act and why they act in that way.
*Main regulator = blood glucose
–Hyperglycaemia (↑ glucose) → ↑insulin
*[e.g. in a post-prandial state]
–Hypoglycaemia (↓ glucose) → ↓ insulin
*Amino acids/fatty acids → ↑ insulin
*Gastrointestinal hormones (“incretins”)
–Ingested food/oral glucose → secretion of GI hormones (e.g. secretin, gastrin, cholecystokinin)
–Above gastrointestinal hormones → ↑ insulin
*Autonomic nervous system (ANS)
–Parasympathetic → ↑ insulin
–Sympathetic (inc. adrenaline) → ↓ insulin
*Stress (e.g. exercise, hypothermia) → ↓ insulin
Diabetes Mellitus - 1
So what happens if insulin regulation goes wrong?
And something which I’m sure you’ve all heard of is diabetes.
And diabetes mellitus, particularly type two is the most common endocrine disorder that we have in human medicine.
And the symptoms of diabetes mellitus. The first one is polyurea, so an increased desire to urinate.
Um, an increased urine production, as a result of the increase urine formation and an increase of thirst.
That’s called polydipsia here, you get A weight loss.
So you’re losing the anabolic effect of insulin because insulin isn’t working properly or is it being secreted.
Therefore, you get a reduction of, anabolism an increase in net catabolism.
And this causes, an overall weight loss. And you can also get urinary tract infection.
So why do you get all these different things. Well.
The reason that you get increased thirst is because you get osmotic diuresis.
So you need to have more water to be able to replace what you’re essentially urinating out of the body.
The polydipsia The increase thirst is because you want to then drink more water to replace what’s been urinated out.
Urinary tract infection.
Well, this is because although your kidneys are normally very efficient at retaining glucose in the blood and not in the urine.
So in a normal, healthy kidney, you don’t have glucose in the urine.
In an untreated patient with diabetes mellitus. If the plasma glucose levels are very high for a long period of time,
you can get some glucose that actually comes out within the urine because the kidney cannot retain it all.
And so if you start having glucose in the urine, then becomes something that’s much more amenable for microorganisms to survive in because the sugar
there and they can live off that and therefore there is an increased risk of urinary tract infection.
And we’ve known about diabetes mellitus for hundreds, if not thousands of years.
And just one quote here, going back 2000 years described it as a melting down of flesh and limbs into urine,
which is not a particularly pleasant description, but largely sums up some of these symptoms quite well.
So before we start looking in a little bit more detail at diabetes, um,
I just want to remind you or inform you of the different types of diabetes that there are.
In this lecture, we are primarily talking about diabetes mellitus.
And diabetes mellitus is the form of diabetes caused by abnormal insulin function and or secretion.
But there is also another form of diabetes which causes an increase of urine production.
But it’s nothing to do with insulin. And that’s called diabetes insipidus.
And this is caused by abnormal secretion of the hormones ADH, antidiuretic hormone,
otherwise referred to as vasopressin from the posterior pituitary gland.
So a completely different cause, a completely different endocrine system that causes this.
The word diabetes essentially tells you that it’s a disease where you get increased urine formation insipidus and mellitus.
The historical reason for these names is the way in which they were diagnosed hundreds of years ago.
Diabetes mellitus. You get some glucose in the urine.
Diabetes insipidus you don’t. And the word mellitus means sweet.
The word insipid means flavourless. And the way hundreds of years ago,
in which clinicians could diagnose between the two forms of diabetes was by having the lovely job of actually tasting a part of the patient’s urine.
If it was sweet, it was diabetes mellitus. If it was flavourless, it was diabetes insipidus.
There are slightly more refined ways of doing it these days, but the basic principle remains.
Diabetes Mellitus - 2
So let’s look at diabetes mellitus. And there are two types of diabetes mellitus that have different causes.
Uh the two types are called type one and type two. Type one diabetes is often referred to as insulin dependent diabetes mellitus.
Um, what is now not a very useful definition, but you might see it in, um, earlier textbooks if you read them.
Sometimes it used to be referred to as early onset diabetes mellitus because it was often found in young adults and in children.
But nowadays that is not a very useful definition, because type two diabetes is being found more and more in younger people.
But what causes type one diabetes is a failure to produce insulin, so you don’t have enough of the hormone secreted.
And just like we’ve seen in other lectures, what can cause an abnormally low amount of hormone production?
Well, one of the main general mechanisms for that is an autoimmune disease.
And indeed type one diabetes mellitus is an autoimmune disease.
And these patients, uh, have an immune system which targets and destroys the beta cells of the islets of Langerhans.
Okay. So the cells that produce and secrete insulin are physically destroyed.
Therefore, these patients cannot make insulin, and therefore they have to be treated by hormone replacement therapy,
which typically is an intramuscular injection of insulin.
So again, you can see similar, um threads going through these different lectures.
Type two diabetes mellitus has a very different cause.
It’s often referred to as non insulin dependent diabetes mellitus, and it’s by far the most common of the two forms of diabetes mellitus.
Again, it’s not particularly useful these days.
But I’ll put it in here because you may see it in your reading.
It used to be referred to as late onset diabetes, because it used to be most common in people in their middle and late adult years.
But because of the increased rise of obesity in younger people, we have an increase,
um, rise in the incidence of type two diabetes mellitus a younger people.
And so the timing, the age of onset is now not a clinically useful distinction.
And the aetiology, which means the cause of the disease is very complex and includes genetics.
Obesity is a very major risk factor, and the way in which the disease develops again is very complex.
We’re not going to go into it in much detail today,
but at least in the early stages of type two diabetes mellitus, the secretion of insulin is relatively normal.
But the disease is caused by what we call insulin resistance.
So this is a lack of sensitivity of the receptors and the lack of ability of the receptors to cause intracellular signalling events.
If insulin binds to it. So insulin can still be secreted in the early stages of type two diabetes,
but its ability to exert its biological effects becomes limited, and if caught,
early stages, dietary advice is part of the treatments that can be given for it,
as well as other drugs that can regulate insulin secretion and insulin sensitivity.
It gets a lot more complex than that, so we’re not going to go into it in any more detail today.
Diabetes Mellitus - 3
Well, I do want to move on to those. One of the consequences of if diabetes is untreated or uncontrolled for a long period of time.
Well, remember what is the main physiological role of insulin.
Well, it’s to stimulate the uptake of glucose from the blood into insulin sensitive tissues,
particularly skeletal muscle, the liver and the white fats.
If we have, um, too much glucose in the blood for a long period of time,
other tissues in the body that would not normally take up glucose from the blood start to absorb some of that glucose.
And these tissues are not designed to effectively and efficiently store that glucose.
And the glucose can cause, um,
quite serious problems because glucose can covalently bind to proteins within these other tissues and modify the function of these proteins.
And this will lead to a number of symptoms such as neuropathy.
So particularly the peripheral nerves um, will start to take up glucose.
In the case of untreated, uh diabetes mellitus.
The glucose binds to proteins within those neurones and reduces the effectiveness of neuronal firing.
And so you can get neuropathy. So, uh, a decreased function of peripheral neurones.
And that can cause a lack of sensitivity, particularly in, uh, peripheral parts of the body such as your hands and your feet.
You can get the formation of cataracts.
So protein glycosylation within the eye, causes cataract formation, which of course is very serious for in terms of vision.
You can also get effects on the kidneys.
And your renal filtration can be, um, disrupted if you get glycosylation of the proteins within your kidney tissue.
So that’s just some of the examples. But these clearly can be very, very serious if left untreated for a long period of time.
In very serious cases you can also get what we call ketoacidosis.
And essentially this refers to the fact that because the body and the metabolic tissues are not taking up as much glucose as they should,
the body starts to use fat for more and more of its energy needs.
Fat metabolism causes the production of what we call ketone bodies, and these cause an increase acidity of the of the body.
And in serious cases, this can cause nausea, vomiting.
In very severe cases, it could even cause a coma. But it’s only typically found in type one diabetes mellitus rather than type two.
So that’s what happens if you have, um, an untreated diabetes.
And so you have too little insulin secretion and or, um, effects on the body.
What about the other way around? What happens if you have too much insulin.
And this can often be caused by, um,
an individual injecting themselves with too much insulin or the wrong time of day relative to their meal schedule.
But if you have too much insulin, what’s the effect of that going to be?
Well, again, remember, the main physiological role of insulin is to remove glucose from the blood into these metabolic tissues.
So if you have too much insulin, you’re likely to get a hypoglycaemia, an abnormally low plasma glucose concentration.
And as a result of this, the body will try and counteract the hypoglycaemia to raise the,
um, the plasma glucose concentration back to homeostatic levels.
And one of the ways in which it does this is by increasing the activity of the sympathetic nervous system and the sympathetic nervous system.
Yes, it will tend to increase the plasma glucose concentration, but it will also do other things.
And so some of the symptoms you get, the cause of this elevated sympathetic nervous system activity include things like sweating and also tachycardia,
which is an abnormally high heart rate. Okay.
So how does this occur? Well, injection of too much insulin or at the wrong time relative to your meals if you’re a type one patient.
But it could also be an individual who has vastly reduced food intake.
Um, or as we’ve seen in other cases, a localised tumour within the beta cells of the islets of Langerhans.
So all in all, diabetes, if uncontrolled, can be a very, very serious condition, particularly for long term health.
The good news is though, if diabetes is well controlled, then these individuals,
these patients can actually live a virtually normal life and a very successful life.
And someone who I’m sure probably very few of you have heard of these days, but I still include them in the lectures, is a guy called Steve Redgrave.
So he was famous because he won gold medals at five different Olympics in rowing, which is, as you probably know, very intensive sports.
And he had diabetes mellitus and he was diagnosed I think, with about halfway through his career.
So even with diabetes mellitus, he was able to go on and become an Olympic gold medallist.
And that just I think shows you that with the right treatments, um, diabetes mellitus can be very well managed.
It’s only if it’s uncontrolled for a long period of time that some of these serious consequences can arise.
Okay. So that’s insulin. It’s structure.
It’s physiological effects. It’s regulation. And what can happen if insulin signalling goes awry.
Glucagon
I now just want to spend a little bit of time mentioning the other main hormone from the islets of Langerhans.
And that is glucagon. And glucagon is produced by the alpha cells of the islets Langerhans.
It’s another peptide hormone. So as should be very clear to you, it’s produced by typical protein synthesis.
It’s stored in granules. It’s released by exocytosis
And really the key thing to say about glucagon is its physiological role is almost directly opposite to that of insulin.
So glucagon tends to increase catabolism, particularly in the liver, causing a breaking down,
particularly of glycogen, to cause the release of glucose from the liver into the blood.
So it stimulates glycogenolysis, which is the breakdown of glycogen.
Um, and to get the balance between insulin, glucose, at least in a fasting individual,
maintains our blood glucose concentration around about 4 to 5 ,mmoles per litre, obviously varies a little bit.
And after a little change in the fasting state, in the healthy individual, that’s about the level that is maintained.
, how does glucagon act? Well, again, it’s a peptide hormone.
So it’s going to act on plus membrane receptors in this case.
.
And what regulates glucagon production. Well, again, plasma glucose concentration is the main thing that glucagon regulates.
So it should be very little surprise to you that plasma glucose is also the main regulator of how much glucagon is secreted.
And in a hypoglycaemic state. So where we have blood glucose levels that start to drop, that is the main stimulator of glucagon secretion.
Overview of Glucose Regulation
So we’ll. I’ve done, um.
Is put this little slide together, which combines what we’ve talked about in terms of the physiology of insulin and, um, glucose.
But it also combines together some of the other hormones that we’ve talked about.
Um, and you will hear about in terms of growth hormone within the physiology module.
So it’s another one of these nice summary diagrams. When you come to revise.
I strongly recommend again that you find these summary diagrams.
You look at them without any other reference to your notes.
If you can explain what’s going on in them, it shows you you understand that part of the module.
Well, so looking at this diagram here, we have blood glucose concentration here in the middle and in the fasting state.
We have a release of glucose from storage molecules into the blood to elevate and maintain blood glucose at a normal homeostatic level.
And the three tissues that we’re looking at skeletal muscle, liver and white fats.
And in skeletal muscle protein is broken down.
But for proteolysis to cause the release of amino acids into the blood and white fat triglycerides are broken down into fatty acids,
which are then released into the blood.
The liver can take up the amino acids, and the fatty acids convert them by a process called gluconeogenesis into new glucose molecules.
The liver also has stores of glycogen within it, and this glycogen can be broken down by glycogenolysis.
This again into glucose, which is then released into the blood.
So these three tissues together acting through the liver as if you like the funnel for um,
for the three of them can release glucose from their stores into the blood to cause a net increase of blood glucose concentration.
What happens if you have an elevated plasma glucose, which in a normal, healthy individual will occur after a meal?
Well, in that case, you want to reduce blood glucose levels from that high postprandial state and lock it away
in these metabolic tissues again to maintain it in a normal homeostatic concentration.
So here we’re looking at skeletal muscle liver and white fat again.
And in this case particularly insulin causes the uptake of glucose into all three of these different tissues.
It also has the anabolic effect of converting glucose into glycogen within skeletal muscle,
glucose into glycogen and fat within the liver, and glucose into fat within the white adipose tissue.
Okay. And the little note the another thing the insulin does that we haven’t got on this slide is it
causes the uptake of amino acids into the skeletal muscle and conversion of them back into proteins.
So a nice overview there of the three main tissues involved in glucose and energy storage,
and the hormones that regulate the movement of glucose in and out of those tissues.
Insulin causes the uptake
glucagon and then the adrenal hormones adrenaline and glucocorticoids, but also growth hormone are all involved in the release of energy from that store into the blood glucose pool itself.
Somatostatin
Very briefly, just in passing, I want to now mention the third islets of Langerhans hormone somatostatin.
And this is another peptide hormone. And this is produced by the delta cells of the islets of Langerhans
Hence um as it’s a peptide it’s produced through the endoplasmic reticulum and Golgi apparatus.
It’s stored in granules. It’s released by exocytosis, all of those same things which you should know immediately.
Um, if you’ve taken on board the week long content.
Um, what does somatostatin do? Well, the first thing that I’ve done here, and also put it in blue,
is that this is one really nice example in physiology of how a single molecule can have very
different physiological effects depending upon what part of the body makes it and is using it.
So hopefully you’ve all looked at the on demand lecture in week one and in the on demand lecture from week one.
I told you that somatostatin can be released from nerve cells in the hypothalamus to inhibit the release of growth hormone from the pituitary gland.
Okay. And that is a bone-a-fide endocrine role of somatostatin these nerve cells in the hypothalamus produce it, release it.
It acts on cells of the anterior pituitary and inhibits growth hormone secretion.
In the context of the endocrine pancreas, somatostatin has a completely different role.
It’s nothing to do with growth hormone okay, so different parts of the body is using the same molecule, somatostatin, and having completely different physiological effects.
So context is really important when you’re thinking about biological signalling molecules and what they do.
And within the pancreas. What somatostatin does is to inhibit the secretion of both insulin and glucagon.
And it does this through a paracrine mechanism.
And this might seem a little bit of a paradox. Why would it decrease the secretion of both these hormones that have completely opposite effects?
And the short answer is not entirely sure. Um, and what has been suggested is that somatostatin is secreted around the time of a meal.
Um, and it’s stimulated by duodenal acid.
And one of the things it probably does is it kind of, prevents exaggerated endocrine responses following a meal. that’s a little bit hand-wavy, because we don’t fully understand what the physiological role is,
and that’s why we’re not covering it in too much detail in this lecture. So that’s somatostatin just very briefly mentioned.
I think the most important thing of this slide is this bit up here.
Just tell you and hopefully remind you that it does a very different role to
its endocrine role at the level of the hypothalamus and the pituitary gland.
Summary
Okay, so before we have, uh, a little quiz to finish off, just a quick summary of the key parts of this lecture.
The pancreas is a highly active secretory tissue,
but it secretes in two different ways the exocrine pancreas and is involved in the release of bicarbonate and enzymes into the duodenum.
So it mixes with the food as it leaves the stomach and enters the small intestine.
But that is not the endocrine part of the pancreas.
The endocrine part of the pancreas is regulated by different parts of the tissue.
The islets of Langerhans and the islets of Langerhans have three main cell types alpha, beta, and delta, and these produce peptide hormones.
Glucagon is a catabolic stimulating hormone produced by the alpha cells.
Insulin is an anabolic hormone produced by the beta cells, and somatostatin we just briefly mentioned is produced by the delta cells.
In terms of what happens when you get abnormal secretion and or function of these hormones.
Well, by far the most relevant, um, pathology here is diabetes mellitus.
Remember, that’s different to diabetes insipidus. Remember the medieval physician sampling people’s, um, urine to tell the difference between the two?
Diabetes mellitus is the most common endocrine disease that we have in man.
It has a very complex aetiology, and aetiology just means the cause of the disease and therefore different treatment.
Um, which I’ve mentioned some of to you today, but you’ll hear a lot more of um in much more detail in pathology lectures later on.
*Are the following statements true or false?
–(a) Type 1 diabetes mellitus can be treated by dietary intervention
–(b) Blood glucose of 8mmol/L would inhibit insulin secretion
–(c) Conversion of glucose to glycogen is an example of a catabolic reaction
Let’s evaluate each of the statements regarding diabetes and metabolic processes:
(a) Type 1 diabetes mellitus can be treated by dietary intervention
False.
Explanation: Type 1 diabetes mellitus is primarily an autoimmune condition where the body’s immune system attacks insulin-producing beta cells in the pancreas. While dietary management is important for overall health and can help manage blood glucose levels, it cannot replace the need for insulin therapy. Individuals with Type 1 diabetes require exogenous insulin to control their blood glucose levels.
(b) Blood glucose of 8mmol/L would inhibit insulin secretion
False.
Explanation: A blood glucose level of 8 mmol/L (which is higher than normal) would actually stimulate insulin secretion, not inhibit it. Insulin is released by the pancreas in response to elevated blood glucose levels to help lower glucose levels by facilitating its uptake into cells and promoting storage as glycogen.
(c) Conversion of glucose to glycogen is an example of a catabolic reaction
False.
Explanation: The conversion of glucose to glycogen is known as glycogenesis, which is an anabolic reaction. Anabolic reactions involve the synthesis of larger molecules from smaller ones, and in this case, glucose molecules are being stored as glycogen.
Summary of Answers
(a) False
(b) False
(c) False
*Why is important to routinely measure urinary protein levels in patients with diabetes mellitus?
So in a normal, healthy individual you don’t get protein in the urine because it’s maintained, um, in the blood by the kidneys.
So if you start to see in a healthy individual, uh, or with an individual,
that protein starts to be expressed and found within the urine, that suggests that the kidneys are not working properly.
Okay. And there are various reasons why that could be.
But in a patient with diabetes mellitus,
if their treatment is not adequate and they have a high level of glucose in their blood for a long period of time,
remember that can be taken up into tissues such as the kidney, cause glycosylation of protein, and therefore inhibits tissue function.
So in a diabetes mellitus patient, if they start to see urine increasing concentration within the urine,
that is a clue that possibly their renal function isn’t as good as it should be, and therefore their diabetes control isn’t as good as it should be.
And so that’s a cue for them to go back to their clinical team and get their condition reviews.
Routine measurement of urinary protein levels in patients with diabetes mellitus is crucial for several reasons:
- Early Detection of Diabetic Nephropathy
Sign of Kidney Damage: Elevated levels of protein in the urine, known as proteinuria, can indicate damage to the kidneys, specifically to the glomeruli (the filtering units of the kidneys). Diabetic nephropathy is a common complication of diabetes, and early detection through urinary protein screening allows for timely intervention. - Monitoring Disease Progression
Progression of Kidney Disease: Regular measurement of urinary protein can help monitor the progression of kidney disease in patients with diabetes. A change in protein levels can indicate worsening kidney function, allowing healthcare providers to adjust treatment plans accordingly. - Assessment of Cardiovascular Risk
Cardiovascular Complications: Diabetic patients with proteinuria are at an increased risk for cardiovascular diseases. Monitoring urinary protein levels helps in assessing overall health and the risk of cardiovascular complications, enabling preventive measures to be taken. - Guiding Treatment Decisions
Treatment Adjustments: If protein levels are found to be elevated, healthcare providers may consider adjusting diabetes management strategies, such as intensifying glycemic control or using medications that have renal protective effects (e.g., ACE inhibitors or ARBs). - Patient Education and Engagement
Encouraging Self-Management: Regular screening for urinary protein levels can engage patients in their health management, highlighting the importance of monitoring diabetes and its complications. It can encourage adherence to treatment and lifestyle modifications.
Summary
In summary, routine measurement of urinary protein levels in patients with diabetes mellitus is essential for the early detection of kidney damage, monitoring the progression of diabetic nephropathy, assessing cardiovascular risk, guiding treatment decisions, and enhancing patient engagement in their healthcare. Early intervention can significantly improve patient outcomes and quality of life.
