HORMONES OF PANCREAS

Hormones of Pancreas is one of the most important topic of Endocrinology.

This post is about a digestive and Exo-endocrine organ known as Pancreas, which is located in abdomen just behind the stomach.

It works as both endocrine (secreting hormones internally like Glucagon, Insulin, Somatostatin and Pancreatic Polypeptide) and Exocrine gland (secreting hormones outside the body or another surface inside the body).

It also secrets some digestive enzymes like Pancreatic Amylase, Lipase and protease etc.

So, let’s get started with its anatomy and at the end of this post we will have brief idea about its hormones and their functions.

FUNCTIONAL ANATOMY OF PANCREAS

The endocrine part of the pancreas has many rounded collections of cells called as pancreatic islets (the islets of Langerhans).

Islets of Langerhans consist of four types of cells that secrete following Hormones,

1. A cells or α(alpha)-cells, which           

    secrete Glucagon.

2. B cells or β(beta)-cells, which 

   secrete Insulin.

3. D cells or δ(delta)-cells, which

   secrete Somatostatin.

4. F cells or PP cells, which

   secrete Pancreatic Polypeptide

GLUCAGON

GLUCAGON HORMONE FUNCTIONS

SOURCE

Secreted by α-cells of Islets of Langerhans.

STRUCTURE

  • Polypeptide (amino acid chains linked with multiple peptide bonds).
  • Composed of 29 amino acids in a single chain.
  • Molecular weight is 3500.

SYNTHESIS

It is synthesized as a proglucagon (precursor of glucagon/ molecular weight 9000), which on constant degradation releases active glucagon.

PLASMA LEVELS, CIRCULATION & DEGRADATION

  • Circulation in plasma is in free form.
  • Basal levels: 100−150 pg/mL.
  • Half-life: 6 min (range 5–9 min).
  • Secretion rate: 100–150 μg/day.
  • Degradation: About 30% of glucagon is degraded in liver and 20% in kidney.

MECHANISM OF ACTION

  • Glucagon binds to the specific receptor on the plasma membrane of target cells.
  • Acts through the interaction of cyclic AMP as a second messenger.

ACTIONS OF GLUCAGON 

1)The actions of Glucagon, are exactly opposite of Insulin.

2) It promotes mobilization of stored nutrients, such as Glucose, Fatty acids and Ketoacids.

3)It increases the blood Glucose(sugar) level,

  • by Increasing Glycogenolysis (Breakdown of glycogen molecule into glucose) in Liver and releasing Glucose from the Liver cells into the Blood.

4) Glucagon does not induce Glycogenolysis in muscle.

5) It Increases Gluconeogenesis (Glucose formation from non- Carbohydrate source) in Liver,

  • By activating the Enzymes, which convert Pyruvate into Phosphoenol Pyruvate.
  • Increasing the transport of amino acids into the Liver cells. Which are utilized for Glucose formation.

6) Glucagon increases the amino acid uptake of liver, which in turn, promotes Gluconeogenesis.

Thus, Glucagon lowers plasma Amino Acids.

7) Glucagon shows Lipolytic and ketogenic actions.

8) It increases Lipolysis by increasing the release of Free Fatty Acids (FFAs).

  • Acids and Glycerol from Adipose tissues into the circulation and making them available for peripheral utilization.
  • In the Liver, excess of FFAs are oxidised resulting in energy production and ketone body synthesis (ketogenesis).

9) It causes Calorigenic effect (Cell consumes more energy to increase Heat generation).

10) Inhibits the secretion of Gastric juice.

11) Increases the secretion of Bile from Liver.

REGULATION OF SECRETION

Controlled mainly by Glucose and Amino Acid levels in the blood.

1) When blood glucose level decreases below 80 mg/dL of blood, α-cells of islets of Langerhans are stimulated and more glucagon is released.

  • Glucagon, in turn increases the blood Glucose level.
  • On the other hand, when Blood Glucose level increases, α-cells are inhibited and the secretion of Glucagon decreases.

2) Increase in amino acid level in blood stimulates the secretion of Glucagon. Which in turn converts the amino acids into Glucose.

3) Factors which increase Glucagon secretion:

Exercise, Stress, Gastrin, Cholecystokinin (CCK), Cortisol.

4) Factors which Inhibit Glucagon secretion: 

Somatostatin, Insulin, Free fatty acids, Ketones.

INSULIN

INSULIN-FUNCTIONS

Historically, insulin is the first hormone to be isolated, purified, crystallized and synthesized.

SOURCE

Insulin is a HORMONE secreted by β-cells in islets of Langerhans of pancreas.

STRUCTURE

  • Insulin is a polypeptide with 51 amino acids.
  • Half-life: 4-6 minutes (In blood).

SYNTHESIS

  • It has two chains called α and β chains.
  • C peptide is a connecting peptide that connects α and β chains.
  • At time of secretion, C peptide is removed.

PREPROINSULIN → PROINSULIN → PEPTIC CLEAVAGE → INSULIN

PLASMA LEVELS

  • Average basal peripheral plasma Insulin level is 10 μU/mL.
  • After several days of fasting, it declines over 50% (less than 5 μU/mL).
  • After prolonged exercise, the plasma Insulin levels fall.
  • A 3–10 time increase in plasma Insulin level is noted after a typical meal. The peak occurs after 30–60 min of initiating the meal.
  • Total daily peripheral delivery of Insulin is about 30 units.

CIRCULATION & DEGRADATION OF INSULIN

  • Insulin circulates free to carrier protein.
  • A protease enzyme, namely insulinase (mainly found in the kidneys and liver), degrade insulin.
  • It splits the disulphide bonds and separates the A and B chains.
  • Very little insulin is excreted unchanged in the urine.

MECHANISM OF ACTION

  • On the target cells, Insulin binds with the receptor protein and forms the Insulin-receptor complex.
  • This complex executes the action by activating the intracellular enzyme system.

ACTIONS OF INSULIN

1) Insulin is Antidiabetic Hormone.

2) It reduces Blood Glucose level by,

  • Increasing transport and uptake of Glucose by cells from blood by increasing permeability of cell membrane to Glucose. 

3) Stimulates rapid uptake of Glucose by all the tissues, particularly liver, muscle and Adipose tissues.

4) Promotes storage of Glucose by Glycogenesis.

5) Inhibits Gluconeogenesis.  

6) Insulin increases synthesis and storage of proteins and inhibits the metabolism of Proteins by:

  • Facilitating the transport of amino acids into cell from blood.
  • Accelerating protein synthesis by increasing the transcription of DNA and by increasing the translation of mRNA.
  • Preventing conversion of proteins into Glucose.

7) Insulin stimulates synthesis of fat. It also increases storage of fat in Adipose tissue.

8) Insulin promotes growth of body.

9) Insulin and Glucagon plays important role in hormonal regulation of Blood Glucose level.

REGULATION OF SECRETION

  • Mainly regulated by Blood Glucose level.
  • Blood glucose level increases, the rate of Insulin secretion.
  • Excess amino acids in blood also stimulate insulin secretion.
  • Ketoacids increase Insulin secretion.
  • Insulin secretion is increased by some of the gastrointestinal hormones such as Gastrin.
  • Parasympathetic stimulation increases Insulin secretion. 
  • Sympathetic nerves inhibit the secretion of Insulin.

Read a detailed post on,

SOMATOSTATIN

SOMATOSTATIN-HORMONES OFPANCREAS

SOURCE OF SECRETION

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

CHEMISTRY & HALF-LIFE

  • Somatostatin is a polypeptide.
  • It is synthesized in two forms (similar in action), –

somatostatin-14 (14 amino acids)

somatostatin-28 (28 amino acids).

  • Half-life: 2 to 4 minutes.

SYNTHESIS

  • From the precursor prosomatostatin.
  • Pro-Somatostatin is converted mostly into somatostatin-14 in the D cells of islets in Pancreas.
  • But in the intestine, large amount of somatostatin-28 is produced from prosomatostatin.

METABOLISM

  • Somatostatin is degraded in Liver and Kidneys.

ACTIONS OF SOMATOSTATIN

1) It inhibits the secretion of both Glucagon and Insulin.

2) It decreases the motility of Stomach, Duodenum and Gallbladder.

3) It reduces the secretion of gastrointestinal hormones gastrin, CCK (cholecystokinin), GIP (gastric inhibitory polypeptide) and VIP (vasoactive intestinal peptide).

4) Hypothalamic somatostatin inhibits the secretion of GH (Growth Hormone) and TSH (Thyroid Stimulating Hormone) from Anterior Pituitary. That is why, it is also called Growth Hormone-Inhibitory Hormone (GHIH).

MODE OF ACTION 

  • Somatostatin acts through c-AMP.

PANCREATIC POLYPEPTIDE

SOURCE OF SECRETION

  • Secreted by PP (Pancreatic Polypeptide) cells in the Islets of Langerhans of Pancreas.
  • It is also found in Small Intestine.

CHEMISTRY & HALF-LIFE

  • Is a Polypeptide with 36 amino acids.
  • Half-life : 5 minutes.

SYNTHESIS

  • Synthesized from Prepropancreatic Polypeptide in the PP cells of Islets.

METABOLISM

  • It is degraded and removed from circulation mainly by Kidneys.

ACTIONS OF PANCREATIC POLYPEPTIDE

  • It increases the secretion of Glucagon from α-cells in Islets of Langerhans.

MODE OF ACTION

  • Pancreatic polypeptide acts through c-AMP.

REGULATION OF SECRETION

  • Secretion of Pancreatic Polypeptide is stimulated by the presence of Chyme (partly digested food from stomach) containing more proteins in the small intestine.
  • Hypoglycemia increases the secretion.
  • While Glucose ingestion decreases the secretion.