 Welcome back to the NPTEL lecture series on animal physiology. So, in the last section we talked about the pancreas and we talked about the exocrine secretions of the pancreas. So, today what we will do we will talk about the endocrine secretion of pancreas. So, in the last class I did the complete anatomy of the pancreas and I showed you the eyelets of Langerhans and within eyelets of Langerhans the alpha cells and the beta cells. So, today we will talk about the different functions endocrine functions of these and how they regulate the glucose metabolism in our body. Just mild recap before we proceed further. So, we are into lecture 5 section of digestive physiology and we are into the section of pancreas and endocrine functions. So, in the last class I drew this. So, I am I am redrawing it for you something like this what we drew. So, these are the duct in the pancreas there are the cells sitting like this. So, these are the asinus and you have some of these cells which are the alpha cells and there are few other cells in close proximity. The structure is more like you know compact structure like this these are the beta cells and then you have this is the cross section I am showing there here the capillaries which are supplying the blood out there and this whole structure is called the. So, this is the recap of the pancreas cross section which I drew last time and I told you that some of these cells are involved in the endocrine function. So, the major hormones which are secreted by pancreas are insulin and glucagon what they do. So, before I draw the schematics try to understand. So, whenever we take any food say for example, you are taking bread or rice or something which is rich in carbohydrates. So, what essentially happens is that carbohydrate is broken down into small sugars the smallest sugar or the functional sugar which body utilizes is glucose could be glucose fructose galactose mannose likewise you know. So, then these glucose. So, so automatically what happens when we are eating. So, within the blood the glucose level shoots up the glucose level shoots up body has to have a mechanism to pull the glucose inside into some storage vessel. Why is it is first of all you understand why there is a why it is essential the body cannot have lot of glucose in the in the in the blood because if the concentration of glucose goes up what essentially happened when the urine is formed. So, urine will have lot of glucose and if urine has lot of glucose in it then glucose will pull a lot of water molecules from your body along with it. So, you will be urinating at a faster rate and you will be losing a lot of water in that process what will happen is that a person will be dehydrated and if this proceeds further the person will have serious problem and this is exactly what happens patient suffering from diabetes. You have heard this word that you know diabetes is kind of very prevalent and as a matter of fact India is the capital is considered as the capital of diabetes because there are way too many diabetes patients in the years to next couple of decades this will be a huge challenge for India. So, essentially body needs a mechanism by which it can pull the glucose those glucose molecules back to some storage area how body does so. So, whenever you are eating there are certain signals which are generated by the nervous system by surrounding cells and everything that request pancreas to secrete insulin and insulin promotes absorption of glucose molecule both by the liver as well as other organ where glucose is converted into glycogen which is a polymer of glucose and much more stable which cannot be utilized directly. So, now this is the major mechanism by which glucose is being pulled out from the blood stream, but now the body is in a starved state body needs glucose suppose you are running for a you are coming from a long distance run or you know you have done a lot of hard work and you do not have glucose at that point in your blood stream. So, there is a opposite set of signals which are generated within the body and those signal leads to the secretion of another hormone which is secreted by the pancreas itself called glucagon. What glucagon essentially does it outsmarts the insulin signal and leads to the breakdown of the glycogen which was stored. So, again the blood glucose level goes up till the body utilizes it for all its maintenance requirement, but again insulin is there it is a check post. So, it is the insulin glucagon check post which regulates the blood sugar level and if there is a problem in this check post then this leads to either hypoglycemia where there is lack of a lack of sugar in the body or hyperglycemia when there is excess sugar in the body in the body means in the blood stream. So, these are the two extreme situation and hyperglycemia or hyperglycemia is being regulated the check post is insulin and glucagon and the master organ which takes care of it is your pancreas. So, this is the overall summary. So, what I will do now I will just draw this thing. So, that it kind of you know gets engraved into your understanding and in future if you want to do an in depth study of this then you can go further. So, coming back. So, these are the and of course we will be highlighting that which cells produce what alpha cells does what beta cells does and how this things all being regulated back to the slides. So, basically what is essentially happening is insulin could be considered insulin could be considered as a primary anabolic hormone. So, since I have introduced this term anabolism anabolic what is the meaning of anabolic there are two words anabolic or catabolic anabolic means when from small small pieces you are building something. So, for example you have individual breaks you are making a building there is an anabolic process catabolism process is that you break the building. So, when the glycogen is forming from individual glucose moiety that is called anabolic anabolism or anabolic activity and when glycogen is broken down into individual glucose components that is called catabolic activity. So, insulin is an anabolic enzyme which leads to the addition of the glucose and likewise to glycogen integration or summation of this leads to the formation of glycogen. So, that is why it is called an anabolic hormone and second thing is that it promotes the storage of the glucose fat and synthesis of protein storage and storage of glucose and fat and synthesis of protein. So, it is secreted by the. So, I showed you that is alpha cells and the beta cells. So, it is the beta cells of the Langer hands in the pancreas which are involved in the secretion of the insulin and this name it has got from a transcription factor this Langer hands cells. So, what regulates it? First and increase as I was telling you increase level of glucose first thing second thing or increase level glucose or amino acids second thing there is a parasympathetic signal signal and the third thing is hormones released by G I tract such as cholecystokinin. So, these are the three major factor which leads to the secretion of insulin, but then what insulin essentially does. So, some of the things what insulin does is that it promotes the diffusion of this glucose moieties into different storage areas maybe in the muscle the liver and several other places. So, let us enumerate those what are the different routes what insulin follows what are the different approaches insulin follows to kind of you know channelize the glucose at different storage units. Let us enumerate that in the slides. So, the first thing it does is stimulate. So, it is a stimulating transport by facilitated diffusion to skeletal muscle where you need a lot of energy to adipose tissue that is in your buttocks and all other places where there is a lot of adipose tissue and insulin also increase the storage of fat as triglyceride in adipose tissue. So, these are the major function of insulin in terms of how it mobilizes the different components of individual units like glucose fatty acids amino acids likewise and eventually in that whole process some of these amino acids are even to glucose. So, these are the overall schematics how the insulin functions secreted by the beta cells of the islets of Langer Hans and what the alpha cells does. So, those are the cells which are involved in the secretion of glucagon. So, let us enumerate the function of glucagon in the slide now. So, glucagon which is basically secreted by the alpha cells of pancreas and this is in response to the secretion is in response to sympathetic innervation sympathetic stimulation. So, here I wish to highlight something if you just remember the previous slide the insulin secretion of the stimulated by the parasympathetic and glucagon stimulation is influenced by the sympathetic. So, I told you while I was teaching is sympathetic and parasympathetic they have opposing function. So, look this is a situation we are on the same organ. So, if I just put it in terms of this is the structure of pancreas. So, it has two sets of innervations which are coming one set which is and other set is like this is how this whole thing is being regulated. So, these are the parasympathetic which are influenced the alpha sorry beta cells and these are sympathetic which are influences the alpha cells. And there is always a dynamic equilibrium between the secretion of alpha and the beta cells which regulates essentially the insulin and glucagon level and that essentially actually controls your. So, once again that is essentially controlling your glucose level it is a very tightly controlled regulated mechanism. So, then what is diabetes? Diabetes is a situation when the beta cells of the anger hands either fail to secrete insulin the capacity to secretion of insulin is compromised or they gets damage because of some situation like pancreas or something like that. So, that is the situation when your body is continuously is unable to regulate the insulin level sorry unable to regulate the glucose level and lot of glucose is being lost through the urine and thereby leading to a excess amount of fluid loss from the body which has its effect. Now, inside it has its effect on the blood volume, on blood pressure, on dehydration, on all every chemical reactions within the body every biochemical reactions within the body. So, if you see a diabetic patient there are lot of complications associated with this whole process. And those complications I think by this time should be clear to you why those complications arise because the blood volume or the water volume is being compromised body is unable to regulate it. So, coming back to the slides. So, this is pretty much is where we are setting and if I had to put it in terms of. So, there are two terms which may you go through different text will come across one is called the fuel flux in fed state. And the second is that fuel flux in the food deprived state. So, both of them explains exactly what I was trying to tell you fuel flux in the fed state. So, when there is a fuel flux. So, in other word what I was telling in the beginning while you take a food it gets broken down by the digestive system into smaller components in the case of proteins and it broken down into amino acids in the case of big lipids it gets broken down into fatty acids a cholesterol. And in case of carbohydrate it broken down into which is the major chunk of our food actually the bulk of our food it gets broken down into simple carbohydrates like glucose, galactose, mannose, maltose likewise. So, that is the situation which we call as the fuel flux and when there is a fuel flux there is a increase in the insulin secretion. And in the next situation when there is a fuel flux in the food deprived state. So, that is the time when a glycogen has to be broken down into small pieces. So, that is when. So, what we talked about is thus this situation fuel flux in the food deprived state is regulated by glucagon and this one is being regulated by insulin. So, this is basically at the two mechanisms which regulates your body's glucose level all the time. And thereby helping you to maintain the balance. And there are two more terms which are of importance are which I have already mentioned is hypoglycemia and there is another called hyperglycemia. Hyperglycemia is a situation when your glucose level is high in the body and hypoglycemia is a situation when glucose level is low in the body. So, based on this the action of insulin and glucagon is regulated. Then how we test all these things in the clinic is something called a glucose tolerance test. What the doctors essentially does is that if the suspicion what they will tell you if they suspect that the glucose metabolism has been compromised in your body what they will tell you do two tests. One is after fasting and one is after feeding. So, what they will do they will ask you that tomorrow morning you come to the clinic or wherever you are giving blood sample. So, they will take a blood sample after the whole night you have an ate anything early morning you go and you give a blood sample. So, the what the doctor will do they will analyze the blood glucose level after fasting this is after fasting. Then they will ask you you take food and come back after two hours this is a situation when you are your body is fairly high in terms of glucose. So, then they will measure the glucose level and then after sometime they will measure again to see whether the glucose level comes back to the original situation or not where it was. So, essentially the chart looks like this droid for you. So, it is something like this if you draw it. So, this is the overnight fast. So, if this is in terms of time in terms of hour and this is we are talking about the glucose tolerance test. So, one hour, two hour, three hour, four hour, five hour likewise. So, this is an overnight fast this is a situation of you have an ate anything during night or after dinner you have an ate anything. So, I am calling that overnight fast after the overnight fast. So, at this point the blood your it shows like this then as soon as you do a fasting it goes up like this and then after three hours it starts falling because this is normal this is how it. So, if somebody picks up sample at this point at this point and at say this point which is fine. So, I know that it has come down to the basal level, but then what happens in a diabetic patients how the profile changes. So, now what I will do I will draw the profile of a person who is having diabetic. So, in the case of diabetic patient the profile goes like this goes like this first of all the basal level is higher and then it goes up and it remain for a long time and cannot come back to its basal level. So, if you look at it is a basal level is somewhere out here for this individual. So, anyway he or she has a higher level and it is a still not coming back whereas, if you look at it in the other situation it has look at it at this time still it is maintaining this is the zone where it is still maintaining whereas, if you look at it this is fairly narrow it is a kind of a tip. So, this is a case of this is a diabetic patient and this is a normal individual and this glucose tolerance test gives you a feel of what exactly is happening in your body. So, what are our options for a person where he or she suffers from diabetes one of the option is that if somewhere or other using stem cell biology could we may pick up any cells of the body and you know make eyelets of longer hands beta cells of eyelets of longer hands and put them back into the pancreas which is a dream approach other than that the only other option which is currently being practiced all over the world. People have to take insulin injection they carry this insulin pouches with them and then they you know they have certain sequence like you know before taking food they take an insulin or just after taking food or before something like that they take the insulin injection to ensure that the glucose molecules are being you know diffused into what I showed you diffused into skeletal muscle into liver and all other places. So, that they could be stored. So, till regenerative medicine has a way to develop alpha cell sorry beta cells of eyelets of longer hands or even alpha cells if somebody has a glucognome problem. So, till that time we are solely dependent on insulin injection. So, that is the state of art currently across the world. So, maybe at time will come when we will have those regenerative medicines where the cells will be able to synthesize we can put the cells back which are beta cells you have the ability to produce insulin. So, this is one aspect. So, from here I will move on to the another major organ which is which plays a very big supporting role in the digestive system is the process of the liver. In case of liver part of it we have done if you recollect while I was showing you how liver has several functions. One of the major function is that liver helps in getting eliminating the byproduct of one of the major byproduct of red blood cell degradation. So, just take a recap and then I will talk about few other things. So, if you remember while we were talking about the red blood cells alive within the bone these red blood cells are formed and these red blood cells have a life of 120 days and I told you after 120 days what essentially happens is that their oxygen carrying capacity is reduced and these red blood cells are being engulfed by the white blood cells. Once they are engulfed into the white blood cells, so red blood cells have this hemoglobin. Hemoglobin having four subunit alpha 1, alpha 2, beta 1, beta 2 and in the center you have a porphyrin ring in each one of these alpha, alpha, beta, beta they have a porphyrin ring within the porphyrin ring there is an iron and it is this iron to which the oxygen binds. So, iron has to be retained back by the body. So, the first thing happens after so this is essentially what happens here. So, these red blood cells come inside this white blood cells which I am showing in yellow. So, here is a red blood cell inside and then what happens is this. So, then this iron Fe 2 plus this iron using different cedar of force is brought back broken down into amino acids which are again brought back to the bones. Whereas, the porphyrin ring porphyrin ring is transformed into bilirubin and then this is made into bilirubin and from here this bilirubin is transported into the organ what we are about to talk is into the liver. So, while actually this reaction of porphyrin ring without. So, the first thing which happens is that from porphyrin the iron is being removed and that process is promoted by oxidation reaction followed by that there is an enzyme called bilirubin reductase which leads to the transformation of bilirubin into bilirubin and then this bilirubin along the blood vessels moves to the liver. In the liver what happens there are two fades which bilirubin meant out here in the liver. So, liver has this canal like structure from where this bilirubin is essentially transported to the large intestine. So, in the large intestine bilirubin is formed into uro bilinogen and then this is transformed into urobulin and this is excreted from the feces. This is one fate and there is other form of bilirubin stericobelinogen, stericobelin and then that is being excreted to the feces there is another fate. So, this is what is all happening is what is happening in the this is all what is happening in the large intestine. So, part of large intestine and this is where the liver is standing. So, liver and this is the large intestine and same by the same root some of these bilirubin goes to the kidney it is secreted via urine. So, this whole process of bilirubin secretion is governed by the liver. So, if the liver ducts have some blockage or their architecture had some problem because of cell damage or something bilirubin secretion is being compromised and bilirubin is yellow in color. So, as soon as you remove the iron from the porphyrin and transform it into bilivaridin this is all yellow. So, that is why see you see in a joint dispassion they are yellowing in their fingers and likewise. So, that basically is because the body fails the liver fails to throw away the bilirubin from the body. So, liver has a lot of role in terms of purifying the toxins from the body and there is another major secretion which is made by the liver that is called bile secretion. So, bile has lot of fat emulsifying action, but what essentially bile is that what are the different composition of the bile includes apart from water. It has different electrolytes than it has as I have already told you it has bilirubin it has steroid hormone it has salts of bile acid it has cholesterol it has lecithin it has phosphatidol choline likewise. So, it is a very complex mixture what is secreted by the liver in the form of bile and this bile has a lot of fat emulsifying actions and it kind of helps assist in the process of digestion. So, this is briefly about the role played by liver and then we are into the last tail piece which is about the large intestine. So, which is a fairly it has a much larger. So, if you look at the cross section it looks like this is the large intestine and in between you see the small intestine which is embedded in between all the. So, this large intestine. So, this is the large intestine here you have the small intestine. So, large intestine is mainly involved in extracting the last bit it has a very limited absorption function as compared to the small intestine, but it ensures as much as electrolytes and water which could be you know conserved by the body one of the major thing it does and apart from it what it does is that it ensures the different this bilirubins and all these things are called transformed into bilirubinogens and everything and being excreted in the form of feces from the body. So, that is pretty much close in our digestive physiology. So, we will be doing little bit more under the heading of metabolism and temperature regulation little bit more which serve a tail pieces which I could not really cover out here. So, but that is give you an overall idea about the role of sympathetic parasympathetic nerves and the role of pancreas role of liver, lower role of a small intestine, endocrine role of pancreas, exocrine role of pancreas and salivary glands and stomach through the conduit tube of esophagus. So, I will close in here. So, we will take over after this on the section on metabolism and temperature regulation there we will just do the rest of the different tail pieces which are left out. Thanks a lot.