Endocrine Functions Of Pancreas Notes

Endocrine Functions Of Pancreas Notes

Islets Of Langerhans

The endocrine function of the pancreas is performed by the islets of Langerhans. The human pancreas contains about 1-2 million islets.

Islets of Langerhans consist of four types of cells:

1. Cells or α cells that secrete glucagon
2. B cells or β cells which secrete insulin
3. D cells or δ cells which secrete somatostatin
4. F cells or PP cells which secrete pancreatic polypeptides.

Read And Learn More: Medical Physiology Notes

Insulin

Source Of Secretion: Insulin is secreted by B cells or the Β cells in the islets of Langerhans of the pancreas.

Chemistry: Insulin is a polypeptide with 51 amino acids and a molecular weight of 5808. It has two amino acid chains called α and β chains which are linked by disulfide bridges. The α chain of insulin contains 21 amino acids, and the β chain contains 30 amino acids.

Plasma Level And Half-Life: The basal level of insulin in plasma is 10 pU /ml. Its biological half-life is 5 minutes.

Functions Of Pancreas

Synthesis:

• Synthesis of insulin occurs in the rough endoplasmic reticulum of β cells in islets of Langerhans. It is synthesized as preproinsulin which gives rise to proinsulin.
• Proinsulin undergoes a series of peptic cleavages leading to the formation of mature insulin and C peptide. C peptide is a connecting peptide that connects α and β chains. At the time of secretion, the C peptide is detached.

Metabolism: The binding of insulin to insulin receptors is essential for removal from circulation and degradation of insulin. Insulin is degraded in the liver and kidney by a cellular enzyme called insulin protease or insulin-degrading enzyme.

Actions Of Insulin: Insulin is an important hormone that is concerned with the regulation of carbohydrate metabolism and blood sugar levels. It is also concerned with the metabolism of proteins and fats.

1. On Carbohydrate Metabolism: Insulin is the only antidiabetic hormone secreted in the body, i.e. it is the only hormone in the body that reduces blood sugar level. Insulin reduces the blood sugar level by its following actions on carbohydrate metabolism:
   1. Increases transport and uptake of glucose by the cells
      • When carbohydrate-rich food is consumed, blood sugar level rises. Immediately, the pancreas secretes insulin. Now, insulin facilitates the transport of glucose from the blood into the cells by increasing the permeability of the cell membrane to glucose.
      • Insulin stimulates the rapid uptake of glucose by all the tissues, particularly the liver, muscle, and adipose tissues. However, insulin is not required for glucose uptake in some tissues like the brain (except the hypothalamus), renal tubules, mucous membranes of the intestine, and RBCs.
      • Insulin also increases the number of glucose transporters, especially GLUT 4 in the cell membrane.
      • Glucose transporters:
        • Usually, glucose is transported into the cells by a sodium-glucose symport pump. In addition to the symport pump, most of the cells have another type of transport protein called glucose transporters (GLUT).
        • So far, seven types of GLUT are identified (GLUT 1-7). Among these, GLUT-4 is insulin sensitive and it is located in cytoplasmic vesicles. It is present in large numbers in muscle fibers and adipose cells.
        • When an insulin-receptor complex is formed in the membrane of such cells, the vesicles containing GLUT- 4 are attracted toward the membrane and GLUT-4 is released into the membrane.
        • Now, GLUT-4 starts transporting the glucose molecules from ECF into the cell. The advantage of GLUT-4 is that it transports glucose at a faster rate.
   2. Promotes peripheral utilization of glucose: Insulin promotes the peripheral utilization of glucose. In the presence of insulin, the glucose that enters the cell is oxidized immediately. The rate of utilization depends upon the intake of glucose.
   3. Promotes storage of glucose – glycogenesis:
      • Insulin promotes the rapid conversion of glucose into glycogen (glycogenesis), which is stored in muscle and liver.
      • Thus, glucose is stored in these two organs in the form of glycogen. Insulin activates the enzymes, which are necessary for glycogenesis. In the liver, when glycogen content increases beyond its storing capacity, insulin causes the conversion of glucose into fatty acids.
   4. Inhibits of glycogenolysis: Insulin prevents the breakdown of glycogen into glucose (glycogenolysis) in muscle and liver.
   5. Inhibits of gluconeogenesis:
      • Insulin prevents gluconeogenesis, i.e. the formation of glucose from proteins by inhibiting the release of amino acids from muscle and by inhibiting the activities of enzymes involved in gluconeogenesis.
      • Thus, insulin decreases the blood sugar level by:
        1. Facilitating transport and uptake of glucose by the
        2. Increasing peripheral utilization of glucose T. increasing the storage of glucose by converting it into glycogen in the liver and muscle
        3. Inhibiting glycogenolysis
        4. inhibiting gluconeogenesis.
2. On Protein Metabolism: Insulin facilitates the synthesis and storage of proteins and inhibits the cellular utilization of proteins.
   • On protein metabolism, insulin:
     1. Facilitates the transport of amino acids into the cell from blood. Insulin actually, increases the permeability of the cell membrane for amino acids
     2. Accelerates the synthesis of proteins by influencing the transcription of DNA and by increasing the translation of mRNA
     3. Prevents the catabolism of proteins by decreasing the activity of cellular enzymes, which act on proteins
     4. Prevents conversion of proteins into glucose. Thus, insulin is responsible for the conservation and storage of proteins in the body.
3. On Fat Metabolism: Insulin stimulates the synthesis of fat. It also increases the storage of fat in the adipose tissue.
   • The actions of insulin on fat metabolism are:
     1. Synthesis of fatty acids and triglycerides: Insulin promotes the transport of excess glucose into cells, particularly the liver cells. This glucose is utilized for the synthesis of fatty acids and triglycerides. Insulin promotes the synthesis of lipids by activating the enzymes which convert:
        • Glucose into fatty acids
        • Fatty acids into triglycerides.
     2. Transport of fatty acids into adipose tissue: Insulin facilitates the transport of fatty acids into the adipose tissue.
     3. Storage of fat: Insulin promotes the storage of fat in adipose tissue by inhibiting the enzymes, which degrade the triglycerides.
4. On Growth: Along with growth hormone, insulin promotes the growth of the body. It is because of its action on the anabolism or proteins. It enhances the transport of amino acids into the cell and the synthesis of proteins in the cells. It also has the protein-sparing effect, i.e. it causes conservation of proteins by increasing the glucose utilization by the tissues.
   • Houssay Animal:
     • The importance of insulin and growth hormone in the growth of the body is demonstrated by the Houssay animal. Houssay animal is the one, in which both anterior pituitary and pancreas are removed.
     • Administration of either insulin or growth hormone alone does not induce growth in this animal. However, the administration of both hormones stimulates growth. This proves the synergistic actions of these two hormones on growth.

Functions Of Pancreas

Mode Of Action Of Insulin: On the target cells, insulin binds with the receptor protein and forms the insulin-receptor complex. This executes the action by activating the intracellular enzyme system. The insulin receptor is a glycoprotein with a molecular weight of 340,000.

• Insulin Receptor: The insulin receptor is present in almost all the cells of the body. The insulin receptor is a tetramer formed by 4 glycoprotein subunits (two α subunits and two β subunits).
  • The α subunits protrude out of the cell and the β subunits protrude inside the cell. The α and β subunits are linked to each other by disulfide bonds. The intracellular surfaces of β subunits have the enzyme activity – protein kinase (tyrosine kinase) activity.
  • When insulin binds with α subunits of the receptor protein, the tyrosine kinase at the β subunit (that protrudes into the cell) is activated by means of autophosphorylation.
  • The activated tyrosine kinase acts on many intracellular enzymes by phosphorylating or dephosphorylating them so that some of the enzymes are activated while others are inactivated.
  • Thus, insulin action is exerted on the target cells by the activation of some intracellular enzymes and by the inactivation of other enzymes.

Regulation Of Insulin Secretion: Insulin secretion is mainly regulated by blood glucose level. In addition, other factors like amino acids, lipid derivatives, gastrointestinal and endocrine hormones, and autonomic nerve fibers also stimulate insulin secretion.

1. Role of Blood Glucose Level
   • When the blood glucose level is normal (80-100 mg/dL), the rate of insulin secretion is low (up to 10 μU/minute). When the blood glucose level increases between 100-120 mg/dL, the rate of insulin secretion rises rapidly to 100 μU /minute.
   • When the blood glucose level rises above 200 mg/dL, the rate of insulin secretion also rises very rapidly up to 400 pU /minute.
   • Biphasic effect of glucose: The action of blood glucose on insulin secretion is biphasic.
     1. Initially, when blood glucose levels increase after a meal, the release of insulin into the blood increases rapidly. Within a few minutes, the concentration of insulin in plasma increases up to 100 pU/ml from the basal level of 10 pU /ml. It is because of the release of insulin that is stored in the pancreas. Later, within 10-15 minutes the insulin concentration in the blood reduces to half the value, i.e. up to 40-50 pU/ml of plasma.
     2. After 15-20 minutes, the insulin secretion rises once again. This time it rises slowly but steadily. It reaches the maximum between 2 and 2V2 hours. The prolonged increase in insulin release is due to the formation of new insulin molecules continuously from the pancreas.
2. Role of Proteins The excess amino acids in the blood also stimulate insulin secretion. The potent amino acids are arginine and lysin. Without any increase in blood glucose level, the amino acids alone can cause a slight increase in insulin secretion. However, the amino acids potentiate the action of glucose on insulin secretion so that, in the presence of amino acids, the elevated blood glucose level increases insulin secretion to a great extent.
3. Role of Lipid Derivatives: The β ketoacids such as acetoacetate also increase insulin secretion.
4. Role of Gastrointestinal Hormones: Insulin secretion is increased by some of gastrointestinal hormones such as gastrin, secretin, cholecystokinin, and GIP.
5. Role of Endocrine Hormones: The hormones like glucagon, growth hormone, and cortisol also stimulate insulin secretion indirectly. All these diabetogenic hormones increase the blood sugar level. The increased blood sugar level stimulates β cells of islets of Langerhans. So insulin secretion is increased.
   • The prolonged hypersecretion of these hormones causes exhaustion of β cells resulting in diabetes mellitus.
6. Role of Autonomic Nerves: The Stimulation of the parasympathetic nerve to the pancreas(right vagus) increases the secretion of insulin.
   • The chemical neurotransmitter involved is acetylcholine. The stimulation of sympathetic nerves inhibits the secretion of insulin, and the neurotransmitter is noradrenaline.
   • However, the role of these nerves on the regulation of insulin secretion under physiological conditions is not clear.

Functions Of Pancreas

Glucagon

Source Of Secretion: Glucagon is secreted from A cells or α cells in the islets of Langerhans of the pancreas. It is also secreted from the A cells of the stomach and L cells of the intestine.

Chemistry And Half-Life: Glucagon is a polypeptide with a molecular weight of 3485. It contains 29 amino acids. The half-life of glucagon is 3-6 minutes.

Synthesis: Glucagon is synthesized from the preprohormone precursor called preproglucagon in the α cells of islets.

Metabolism: About 30% of glucagon is degraded in the liver and 20% in the kidney. The cleaved glucagon fragments are excreted through urine. Fifty percent of the circulating glucagon is degraded in the blood itself by enzymes such as serine and cysteine proteases.

Actions Of Glucagon: Actions of glucagon are antagonistic to those of insulin. It increases the blood sugar level, increases the peripheral utilization of lipids, and facilitates the conversion of proteins into glucose.

1. On Carbohydrate Metabolism: Glucagon increases the blood glucose level.
   Glucagon
   1. Increases glycogenolysis in the liver. And, the glucose thus formed is released from the liver cells into the blood. Glucagon does not induce glycogenolysis in muscle
   2. Increases gluconeogenesis in the liver. It promotes gluconeogenesis by
      • Activating the enzymes, which convert pyruvate into phosphoenol pyruvate
      • Increasing the transport of amino acids into the liver cells. The amino acids are utilized for glucose formation.
2. On Protein Metabolism: Glucagon increases transport of amino acids into liver cells The amino acids are utilized for gluconeogenesis.
3. On Fat Metabolism: Glucagon shows lipolytic and ketogenic actions. It increases lipolysis by increasing the release of free fatty acids from adipose tissue and making them available for peripheral utilization. The lipolytic activity of glucagon, in turn, promotes ketogenesis (formation of ketone bodies) in the liver.
4. Other Actions Glucagon:
   1. Inhibits the secretion of gastric juice
   2. Increases the secretion of bile from the liver.

Mode Of Action Of Glucagon; On the target cells (mostly liver cells) glucagon combines with receptors and activates adenyl cyclase via G protein. Adenyl cyclase causes the formation of cyclic AMP which brings out the actions of glucagon. Glucagon receptor is a peptide with a molecular weight of 62000.

Regulation Of Glucagon Secretion: The secretion of glucagon is controlled mainly by blood glucose and amino acid levels in the blood.

1. Role of Blood Glucose Level: The important factor that regulates the secretion of glucagon is the decrease in blood glucose level. When blood glucose level decreases below 80 mg/dL of blood, α cells of islets of Langerhans are stimulated, and more glucagon is released. The glucagon in turn increases the blood glucose level. On the other hand, when the blood sugar level increases, cells are inhibited and the secretion of glucagon decreases.
2. Role of Amino Acid Level in Blood: An increase in amino acid level in blood stimulates the secretion of glucagon. Glucagon, in turn, converts the amino acids into glucose.
3. Role of Other Factors:
   • Factors that increase glucagon secretion:
     1. Exercise
     2. Stress
     3. Gastrin
     4. Cholecystokinin
     5. Cortisol.
   • Factors that inhibit glucagon secretion:
     1. Somatostatin
     2. Insulin
     3. Free fatty acids
     4. Ketones.

Somatostatin

Source Of Secretion: Somatostatin is secreted from:

1. Hypothalamus
2. D cells (δ cells) in islets of Langerhans of the pancreas
3. D cells in the stomach and upper part of the small intestine.

Chemistry And Half-Life: Somatostatin is a polypeptide. It is synthesized in two forms namely, somatostatin – 14 (with 14 amino acids) and somatostatin-28 (with 28 amino acids). Both forms have similar actions. The half-life of somatostatin is 2-4 minutes.

Synthesis: Somatostatin is synthesized from the precursor prosomatostatin. Prosomatostatin is converted mostly into somatostatin-14 in the D cells of islets in the pancreas.

• However, in the intestine, a large amount of somatostatin-28 is produced from pro-somatostatin.
• The metabolism of somatostatin is not clearly understood.

Actions Of Somatostatin

1. Somatostatin acts within islets of Langerhans and, inhibits a and (3 cells, i.e. it inhibits the secretion of both glucagon and insulin
2. It decreases the motility of the stomach, duodenum, and gallbladder
3. It reduces the secretion of gastrointestinal hormones gastrin, CCK, GIP, and VIP
4. Hypothalamic somatostatin inhibits the secretion of GH and TSH from the anterior pituitary. That is why, it is also called growth hormone inhibitory hormone (GHIH).

Mode Of Action Of Somatostatin: Somatostatin brings out its actions through cAMP.

Regulation Of Secretion Of Somatostatin: The secretion of pancreatic somatostatin is stimulated by glucose, amino acids, and cholecystokinin. The tumor of 0 cells of islets of Langerhans causes hypersecretion o! somatostatin. It leads to hyperglycemia and other symptoms of diabetes mellitus.

• The secretion of somatostatin in Gl tract increases by the presence of chyme containing glucose and proteins In and small intestine.

Functions Of Pancreas

Pancreatic Polypeptide

• Source Of Secretion: Pancreatic polypeptide is secreted by F cells or PP cells in the islets of Langerhans of the pancreas. It is also found in the small intestine.
• Chemistry And Half-Life: It is a polypeptide with 36 amino acids. Its half-life is 5 minutes.
• Metabolism: Pancreatic polypeptide is degraded and removed from circulation mainly in the kidney.
• Actions: The exact physiological action of pancreatic polypeptide is not known. It is believed to increase the secretion of glucagon from α cells in islets of Langerhans.
• Mode Of Action Of Pancreatic Polypeptide: Pancreatic polypeptide brings out its actions through cAMP.
• Regulation Of Secretion: Secretion of pancreatic polypeptide is stimulated by the presence of chyme containing more proteins in the small intestine.

Regulation Of Blood Sugar Level Blood Glucose Level

Normal Blood Sugar Level

• In normal persons, blood sugar level is controlled within a narrow range. In the early morning after overnight fasting, the blood sugar level is low ranging between 70 and 110 mg/dL of blood.
• Between the first and second hour after meals (postprandial), the blood sugar level rises to 100-140 mg/dL. The sugar level in the blood is brought back to normal at the end of the second hour after the meals.
• In normal persons, the blood sugar is well maintained in spite of the lack of dietary sources. The blood sugar regulating mechanism is operated through the liver one muscle by the influence of the pancreatic hormones insulin and glucagon.
• Many other hormones are ai-e involved in the regulation of blood sugar levels. Amor-gall the hormones, insulin is the only hormone that reduces the blood sugar level and it is called the antidiabetogenic hormone. The hormones, that increase blood sugar levels, are called diabetogenic hormones or anti-insulin hormones.
• The necessity of Regulation of Blood Glucose Level: Regulation of blood sugar (glucose) level is very essential because, glucose is the only nutrient that is utilized for energy by many tissues such as brain tissues, retina, and germinal epithelium of the gonads.

Role Of the Liver In The Maintenance Of Blood Sugar Levels: The liver serves as an important glucose buffer system. When blood sugar level increases after a meal, the excess glucose is converted into glycogen and stored in the liver. Afterward, when the blood sugar level falls, the glycogen in the liver is converted into glucose and released into the blood. The storage of glycogen and release of glucose from the liver is mainly regulated by insulin and glucagon.

Role Of Insulin In The Maintenance Of Blood Sugar Level: Insulin decreases the blood sugar level and it is the only antidiabetic hormone available in the body.

Role Of Glucagon In The Maintenance Of Blood Sugar Level: Glucagon increases the blood sugar level.

Role Of Other Hormones In The Maintenance Of Blood Sugar Levels: The other hormones that increase the blood sugar levels are

1. Growth hormone
2. Thyroxine
3. Cortisol
4. Adrenaline

Thus, the liver helps to maintain the blood sugar level by storing glycogen when the blood glucose level is high after meals and by releasing glucose when the blood sugar level is low after 2-3 hours of food intake. Insulin helps to control the blood sugar level, especially after meals, when its is increases. Glucagon and other hormones help to maintain the blood sugar level by raising it in between meals.