The Potent Pancreas

Warm Greetings!

In this article, I would like to throw some light on one of the most important glands in our body which performs a huge range of functions. As you must’ve guessed it from the title, I’m speaking about the Pancreas. Pancreas is associated with management of our dietary macronutrients including Carbohydrates, Proteins and Fat. Based on our eating habits as well as the frequency of eating meals, pancreas can work either constructively or destructively. Before we dive deep into the anatomy of pancreas, we must understand some key definitions;

    a) Gland – A gland is basically an organ of our body which is capable of secreting chemical substances that are known to perform specific functions. 

                 
Based upon the mode of releasing its chemical contents, we have two types of glands in general – Exocrine and Endocrine.

Exocrine glands are known to release certain enzymes for breaking down our macronutrients and release these enzymes through certain pancreatic ducts into the small intestine.  

Endocrine glands on the other hand are ductless glands and release certain Hormones directly into the bloodstream.  

     b) Hormones: Hormones are chemical messengers in our bodies that help in communicating between organs through the bloodstream. It is basically our internal mobile device which utilizes chemical molecules as a sim-card for signalling. Examples of our Hormones – Growth Hormone, Sex hormones like Testosterone, Progesterone, Estrogen, glucocorticoids, mineralocorticoids and many more. 

Anatomy:

Pancreas is an extremely small glandular organ with a length of 15-20cms and weighing approximately about 75-100gms. It is located on the left side in an oblique position starting from the Duodenum (Beginning of small intestine) and ending on the hilum of the spleen.

The pancreas is differentiated into four main parts – Head, Neck, Body and Tail. As you can see from the diagram below, the head of the pancreas is located in the C-loop formed from the Duodenum and the tail attaches to the spleen.

    
Pancreas is considered to be an all-rounder as it possesses exocrine as well as endocrine functions. The pancreatic cell mass consists of 85% Exocrine, 2% Endocrine, 10% Extracellular matrix and the remaining 3% belongs to Ducts and vessels.

Let’s talk about the exocrine functions of pancreas which make up such a vast majority of the pancreatic cell mass. ‘Acinar Cells’ form the exocrine part of the pancreas. These cells are pyramidal in shape and are present within the ‘Acinus’ compartment. Each compartment has approximately 40 acinar cells. 

                     

These acinar cells release certain digestive enzymes which breaks down the starches, proteins and fats present in our meals. These digestive juices are poured into the small intestine via the main pancreatic duct known as the Duct of Wirsung. This duct is kept in check by a valve known as the Ampulla of Vater. The common Bile duct from the gall bladder pours Bile into the small intestine which breaks down specifically fats in our meal.

          

The digestive juice chiefly involves the following enzymes,

Enzyme	Secretion Form	Functions
Amylase	It is secreted in an active form.	Amylases break down the starch in our foods to simple sugars like Dextrins and Maltose. Maltose is further broken down to ‘Glucose’ by intestinal enzyme – Maltase.
Proteases like Trypsin, Chymotrypsin, Carboxypeptidase A and B, Elastase, Intestinal peptidases etc.	They are secreted as pro-enzymes (inactive) and are activated in the duodenum (Small intestine). If they are activated within the pancreas, they would start degrading the pancreas itself.	Proteases break down the proteins in our meal into individual amino acids (They are the building blocks of Proteins) and smaller peptides (Small chains of amino acids). These peptides further activate certain chemicals like Cholecystokinin, secretin from the endocrine cells which in turn stimulate the release of more digestive juice.
Lipases	They are secreted in an active form.	Lipases break down the fats from our foods into individual fatty acids and glycerol.

Following diagram would help you understand the release of different enzymes clearly, 



The pancreas starts a response to a meal in three phases;

     a)  Cephalic Phase – This phase accounts for 10% of a meal-induced pancreatic secretion which occurs in response to sight, smell and taste of a food.
So the next time, someone says they are getting fat just by looking at food, you know they are completely wrong.

    b) Gastric Phase – It accounts for 10% of a meal –induced pancreatic secretion and primarily occurs after a stomach distension (Ballooning) after a meal.

    c) Intestinal Phase – It accounts for 80% of all the phases and it results in release of all the pancreatic juices.

The acinar cells of the exocrine gland are not specialised as compared to the endocrine gland, thus produce all the enzymes through a single cell.

Let us now move on to the Endocrine function of the pancreas which is the most vital part of the pancreatic cell mass even though it makes up only 2% of the entire pancreas.

Small clusters of endocrine cells known as the ‘Islets of Langerhans’ are located within the acinus compartment of the pancreas which also possess the acinar cells. These islets are classified into four main types – α cells, β cells, δ cells and F cells.

β cells – They make up about 75% of the Islets of Langerhans and produce ‘Insulin’ hormone

α cells – They make up about 20% of the Islets of Langerhans and produce ‘Glucagon’ hormone which is known as an opposing hormone to Insulin.

δ cells – They make up the remaining 5% of the Islets and are known to produce ‘Somatostatin’ hormone.

F cells – They produce intestinal polypeptides (PP).  

     

The β cells are located in the centre surrounded by the α cells and δ cells. Our body possesses 1 million islets with approximately 3000 α, β and δ cells in each islet. This seems so huge but the entire islet cell mass makes up about only 1gm in a single pancreas. This is just amazing!

Let us now speak about the various hormones that these cells secrete.

INSULIN from β Cells :

Insulin, as we have all heard, is one of the most dominant hormones in our bodies. Insulin is a 56 - amino acid polypeptide with α chain and β chain linked by two disulphide bridges between the two chains. Insulin is converted from Proinsulin (Inactive) to its active form by cleavage of C – peptide between the α and β chains.

    

Insulin is secreted in response to high blood plasma concentration of Glucose after a high-carbohydrate meal. The maximum insulin release is when the blood plasma concentrations of glucose reaches around 400 mg/dL.

At this moment, glucose enters into the pancreatic β cells. Now glucose is hydrophilic which means it is water soluble in nature. It cannot pass the cell membrane which is made of a phospholipid bilayer (Fat). Hence glucose requires a transporter (not Jason Statham) to enter into the cells.

There are four different types of glucose transporters;

GLUT1 is generally expressed in the state of fasting and it has a much higher affinity for glucose molecules. GLUT2 is generally expressed after a meal when the plasma glucose concentration is quite high. These receptors have a much lower affinity for glucose. GLUT3 is expressed in Neuronal Cells and GLUT4 in the muscle cells

When glucose enters into the pancreatic β cells via the glucose transporter, it primarily undergoes a phosphorylation (addition of a Phosphate group) which leads to the formation of Glucose-6-phosphate. This form of Glucose can then undergo various pathways like Glycolysis (To create energy in the form of ATP), Glycogen synthesis (Stored form of Glucose in the Liver and the muscles) and finally lipogenesis (Fat storage).

When there is production of energy through Glycolysis and Krebs cycle, an increase in ATP leads to closure of the K⁺ ion channels and opening of Ca²⁺ ion channels which ultimately lead to increase in the cellular calcium levels which triggers Insulin release.

In addition to this, certain other chemicals like cholesystokinin, acetylcholine, Gastric Inhibitory peptide (GIP), glucagon, glucagon like peptide (GLP-1) can amplify the release of Insulin.

Once Insulin is released by such triggers, its primary role is to lower the blood glucose concentration. Insulin attaches to the insulin receptor (Heterotetramer) on the cell membranes and allows the entry of glucose, amino acids and other minerals into the cells. Hence, Insulin plays a vital role in the entry of nutrients inside the cells. Thus Insulin also helps in building of muscles by providing the entry of amino acids into the cells.

Insulin has quite an important role in the storage of glucose in the form of Glycogen. Glycogen is stored inside the Liver upto 100gms and inside the muscles upto 400gms. Upon reaching this limit of storage, Insulin starts converting the excess glucose into triglycerides by linking the free fatty acids to a molecule of glycerol in adipocytes (Fat cells)

In order to understand this clearly, Glycogen (Stored Glucose) might be compared to food in our refrigerator to which we have quite an easy access. On the other hand, Fat might be compared to the products in the grocery store that are not readily available to us (But we can surely tap into it). Since insulin is chiefly involved in storage, it would inhibit all other processes that lead to production of new glucose either from Glycogen (Glycogenolysis) or from non-carbohydrate sources (Gluconeogenesis)

Glucagon from α Cells:

Glucagon is a 29 - amino acid single chain peptide that counteracts the working of Insulin. As compared to Insulin which is released during meals, Glucagon is released in the state of fasting. Glucagon maintains the blood glucose levels by creating new glucose from the breakdown of Glycogen or proteins and fats.

Breakdown of Glycogen essentially occurs from the Liver which has around 100gms of stored glucose. This stored form of glucose can be exhausted within 24 hours of fasting.

Glucagon is inhibited by high levels of Insulin as well as high levels of plasma glucose.

Somatostatin from δ cells:

Somatostatin is a peptide that has two bioactive forms – 14 amino acid and 28 amino acid. This hormone specifically blocks the exocrine as well as endocrine secretions from the pancreas.

Pancreatic Polypeptide (PP) from F cells:

Pancreatic polypeptide is a 36 - amino acid peptide that plays a vital role in inhibiting Bile secretion, gallbladder contraction and exocrine pancreatic secretion. Bile helps in the breakdown of fats.

In order to trigger the release of this peptide, one must consume moderate protein and fat in their meals.

As you can clearly understand from the diagram below, our normal blood plasma glucose is in the range of 70-90 mg/dL. The body would do anything and everything to maintain this range as any alterations in the blood glucose levels would be detrimental in the long term.

      

When the plasma glucose concentrations rises above the normal range, Insulin is triggered by the pancreatic β cells and it starts lowering the blood glucose by allowing its transfer into the cells. Orally taken glucose has a much higher Insulin response as compared to intravenously administered glucose chiefly due to additional hormones (GIP, GLP-1) that potentiate Insulin secretion.

Upon constant Insulin being released by consumption of high-carbohydrate meals, the number of Insulin receptors expressed on the Liver start going down. Due to this, less Insulin is accepted and this creates ‘Insulin resistance’. Insulin resistance is a condition in which there’s high levels of Insulin (hyperinsulinemia) and high levels of glucose (hyperglycemia) in the blood.

Overtime chronic hyperglycemia and hyperinsulinemia (High Insulin) have many adverse effects on the body, ultimately leading to Diabetes Mellitus (Type 1 and Type 2)

        

When I say overtime, it means that the body takes around 20 years to even start showing symptoms of hyperglycemia. Until then, the body keeps on increasing insulin and cramming sugar, ultimately resulting in Insulin exhaustion (Type 1 Diabetes)

In this way, the body keeps on taking hits due to the bad food choices that we take, and we face the repercussions in the long run.

Am I taking this too far or making it a big deal? Let’s just look over statistics for a little bit. India is home to 77 million Diabetics making it the second largest country after China to have such high cases of Diabetes. I don’t think we are doing fine at all.

On top of this, whenever we try to get tested for Diabetes, we are only tested for high blood sugars and not Insulin. Insulin and Blood sugars are both related closely and if there is a problem with Blood sugars, there would definitely be a problem with Insulin and vice versa.

So instead of directly taking external insulin which would make the situation worse, one must focus on correcting Insulin resistance. I would discuss the ways of doing it in my next article by improving glycemic control gradually and thus improving Insulin response.   

Reference:

·  The Netter Collection of Medical Illustrations, Second Edition, Volume 2- Endocrine System.