Pancreas Endocrine Functions .
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| pancreas . |
[1]. Pancreas acts as digestive organ and hormonal Function .Pancreas secretes digestive enzymes as well as endocrine hormones ,Which helps in digestion .
[2]. Pancreas perform both Endocrine as well as Exocrine function . Islets of Langerhans of Pancreas play Endocrine Function .
[3]. Few Pancreatic cells secretes hormones Which helps in control and regulates blood-glucose level in the body .
[4]. The endocrine Portion of Pancreas are a discrete unit of Langerhans , Which Composed of 5 different types of pancreatic endocrine cell .
[5]. These pancreatic endocrine cell are :-
a. Alpha .
b. Beta .
c. Delta .
d. Epsilon .
e. Upsilon .
[6]. Pancreatic endocrine cell secretes hormone are Glucagon , insulin , Somatostatin , Ghrelin and Pancreatic Polypeptide respectively .
Islets of Langerhans .
[1]. Endocrine function of pancreas is performed by the islets of Langerhans.
[2]. Human pancreas contains about 1 to 2 million islets.
[3]. Islets of Langerhans consist of four types of cells:
1. A cells or α-cells, which 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 polypeptide.
Insulin .
Source of Secretion of Insulin .
Insulin is secreted by B cells or the β-cells in the islets of Langerhans of pancreas.
Chemistry & Half-life of Insulin .
[1]. Insulin is a polypeptide with 51 amino acids and a molecular weight of 5,808.
[2]. It has two amino acid chains called α and β chains, which are linked by disulfide bridges.
[3]. The α-chain of insulin contains 21 amino acids and β-chain contains 30 amino acids.
[4]. The biological half-life of insulin is 5 minutes.
Plasma Level of Insulin .
Basal level of insulin in plasma is 10 µU/mL.
Synthesis of Insulin .
[1]. Synthesis of insulin occurs in the rough endoplasmic reticulum of β-cells in islets of Langerhans.
[2]. It is synthesized as preproinsulin, that gives rise to proinsulin.
[3]. Proinsulin is converted into insulin and C peptide through a series of peptic cleavages.
[4]. C peptide is a connecting peptide that connects α and β chains. At the time of secretion, C peptide is detached.
[5]. Pre-proinsulin → Proinsulin Peptic cleavage → Insulin
Metabolism of Insulin .
[1]. Binding of insulin to insulin receptor is essential for its removal from circulation and degradation. [2]. Insulin is degraded in liver and kidney by a cellular enzyme called insulin protease or insulin-degrading enzyme.
Actions of Insulin .
[1]. Insulin is the important hormone that is concerned with the regulation of carbohydrate metabolism and blood glucose level.
[2]. It is also concerned with the metabolism of proteins and fats.
1. On Carbohydrate Metabolism .
[1]. Insulin is the only antidiabetic hormone secreted in the body, i.e. it is the only hormone in the body that reduces blood glucose level.
[2]. Insulin reduces the blood glucose level by its following actions on carbohydrate metabolism:
i. Increases transport and uptake of glucose by the cells .
[1]. Insulin facilitates the transport of glucose from blood into the cells by increasing the permeability of cell membrane to glucose.
[2]. Insulin stimulates the rapid uptake of glucose by all the tissues, particularly liver, muscle and adipose tissues. But, it is not required for glucose uptake in some tissues such as brain (except hypothalamus), renal tubules, mucous membrane of intestine and RBCs.
[3]. Insulin also increases the number of glucose transporters, especially GLUT 4 in the cell membrane.
Glucose transporters .
[1]. Usually, glucose is transported into the cells by sodium-glucose symport pump. In addition to symport pump, most of the cells have another type of transport proteins called glucose transporters (GLUT). So far, seven types of GLUT are identified (GLUT 1–7).
[2]. Among these, GLUT4 is insulin sensitive and it is located in cytoplasmic vesicles. It is present in large numbers in muscle fibers and adipose cells.
[3]. When insulin-receptor complex is formed in the membrane of such cells, the vesicles containing GLUT4 are attracted towards the membrane and GLUT4 is released into the membrane.
[4]. Now, GLUT4 starts transporting the glucose molecules from extracellular fluid (ECF) into the cell. The advantage of GLUT4 is that it transports glucose at a faster rate.
ii. Promotes peripheral utilization of glucose .
[1]. Insulin promotes the peripheral utilization of glucose.
[2]. In presence of insulin, glucose which enters the cell is oxidized immediately.
[3]. The rate of utilization depends upon the intake of glucose.
iii. Promotes storage of glucose – glycogenesis .
[1]. Insulin promotes the rapid conversion of glucose into glycogen (glycogenesis), which is stored in the muscle and liver. Thus, glucose is stored in these two organs in the form of glycogen.
[2]. Insulin activates the enzymes which are necessary for glycogenesis.
[3]. In liver, when glycogen content increases beyond its storing capacity, insulin causes conversion of glucose into fatty acids.
iv. Inhibits glycogenolysis .
Insulin prevents glycogenolysis, i.e. the breakdown of glycogen into glucose in muscle and liver.
v. Inhibits gluconeogenesis .
[1]. 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.
[2]. Thus, insulin decreases the blood glucose level by:
1. Facilitating transport and uptake of glucose by the cells .
2. Increasing the peripheral utilization of glucose .
3. Increasing the storage of glucose by converting it into glycogen in liver and muscle .
4. Inhibiting glycogenolysis .
5. Inhibiting gluconeogenesis.
2. Protein metabolism .
Insulin facilitates the synthesis and storage of proteins and inhibits the cellular utilization of proteins by the following actions:
1. Facilitating the transport of amino acids into the cell from blood, by increasing the permeability of cell membrane for amino acids
2. Accelerating protein synthesis by influencing the transcription of DNA and by increasing the translation of mRNA
3. Preventing protein catabolism by decreasing the activity of cellular enzymes which act on proteins
4. Preventing conversion of proteins into glucose. Thus, insulin is responsible for the conservation and storage of proteins in the body.
3. Fat Metabolism .
Insulin stimulates the synthesis of fat. It also increases the storage of fat in the adipose tissue.
Actions of insulin on fat metabolism are :-
i. Synthesis of fatty acids and triglycerides .
[1]. Insulin promotes the transport of excess glucose into cells, particularly the liver cells.
[2]. This glucose is utilized for the synthesis of fatty acids and triglycerides.
[3]. Insulin promotes the synthesis of lipids by activating the enzymes which convert:
a. Glucose into fatty acids .
b. Fatty acids into triglycerides.
ii. Transport of fatty acids into adipose tissue .
Insulin facilitates the transport of fatty acids into the adipose tissue.
iii. Storage of fat .
Insulin promotes the storage of fat in adipose tissue by inhibiting the enzymes which degrade the triglycerides.
4. On Growth .
[1]. Along with growth hormone, insulin promotes growth of body by its anabolic action on proteins.
[2]. It enhances the transport of amino acids into the cell and synthesis of proteins in the cells.
[3]. It also has the protein-sparing effect, i.e. it causes conservation of proteins by increasing the glucose utilization by the tissues.
Houssay Animal .
[1]. The importance of insulin and growth hormone in the growth of the body is demonstrated by Houssay animal.
[2]. Houssay animal is one in which both anterior pituitary and pancreas are removed.
[3]. Administration of either insulin or growth hormone alone does not induce growth in this animal. However, the administration of both the hormones stimulates the growth. This proves the synergistic actions of these two hormones on growth.
Mode of Action of Insulin .
[1]. On the target cells, insulin binds with the receptor protein and forms the insulin-receptor complex. [2]. This complex executes the action by activating the intracellular enzyme system.
Insulin Receptor .
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| Structure of Insulin receptor . |
[1]. Insulin receptor is a glycoprotein with a molecular weight of 340,000.
[2]. It is present in almost all the cells of the body.
Subunits of insulin receptor .
[1]. Insulin receptor is a tetramer, formed by four glycoprotein subunits (two α-subunits and two β-subunits).
[2]. The α-subunits protrude out of the cell and the β-subunits protrude inside the cell .
[3]. The α and β subunits are linked to each other by disulfide bonds.
[4]. Intracellular surfaces of α-subunits have the enzyme activity – protein kinase (tyrosine kinase) activity.
[5]. 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.
[6]. 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.
[7]. 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 .
[1]. Insulin secretion is mainly regulated by blood glucose level.
[2]. 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 .
[1]. When blood glucose level is normal (80 to 100 mg/dL), the rate of insulin secretion is low (up to 10 µU/minute).
[2]. When blood glucose level increases between 100 and 120 mg/dL, the rate of insulin secretion rises rapidly to 100 µU/minute.
[3]. When blood glucose level rises above 200 mg/dL, the rate of insulin secretion also rises very rapidly up to 400 µU/minute.
Biphasic effect of glucose .
Action of blood glucose on insulin secretion is biphasic.
1. Initially, when blood glucose level increases after a meal, the release of insulin into blood increases rapidly.
[1a]. Within few minutes, concentration of insulin in plasma increases up to 100 µU/mL from the basal level of 10 µU/mL.
[1b]. It is because of release of insulin that is stored in pancreas. Later, within 10 to 15 minutes, the insulin concentration in the blood reduces to half the value, i.e. up to 40 to 50 µU/mL of plasma.
2. After 15 to 20 minutes, the insulin secretion rises once again. This time it rises slowly but steadily.
[2a]. It reaches the maximum between 2 and 2½ hours.
[2b]. The prolonged increase in insulin release is due to the formation of new insulin molecules continuously from pancreas .
2. Role of Proteins .
[1]. Excess amino acids in blood also stimulate insulin secretion. Potent amino acids are arginine and lysin.
[2]. Without any increase in blood glucose level, the amino acids alone can cause a slight increase in insulin secretion.
[3]. However, amino acids potentiate the action of glucose on insulin secretion so that, in the presence of amino acids, 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 the gastrointestinal hormones such as gastrin, secretin, CCK and GIP.
5. Role of Endocrine Hormones .
[1]. Diabetogenic hormones like glucagon, growth hormone and cortisol also stimulate insulin secretion, indirectly.
[2]. All these diabetogenic hormones increase the blood glucose level, which stimulates β-cells of islets of Langerhans. So insulin secretion is increased.
[3]. Prolonged hypersecretion of these hormones causes exhaustion of β-cells, resulting in diabetes mellitus.
6. Role of Autonomic Nerves .
[1]. Stimulation of parasympathetic nerve to the pancreas (right vagus) increases insulin secretion.
[2]. Chemical neurotransmitter involved is acetylcholine.
[3]. Stimulation of sympathetic nerves inhibits the secretion of insulin and the neurotransmitter is noradrenaline.
[4]. However, the role of these nerves on the regulation of insulin secretion under physiological conditions is not clear.
Glucagon .
Source of Secretion of Glucagon .
[1]. Glucagon is secreted from A cells or α-cells in the islets of Langerhans of pancreas.
[2]. It is also secreted from A cells of stomach and L cells of intestine.
Chemistry & Half-life of Glucagon .
[1]. Glucagon is a polypeptide with a molecular weight of 3,485.
[2]. It contains 29 amino acids.
[3]. Half-life of glucagon is 3 to 6 minutes.
Synthesis of Glucagon .
[1]. Glucagon is synthesized from the preprohormone precursor called preproglucagon in the α-cells of islets.
[2]. Preproglucagon is converted into proglucagon, which gives rise to glucagon.
Metabolism of Glucagon .
[1]. About 30% of glucagon is degraded in liver and 20% in kidney.
[2]. The cleaved glucagon fragments are excreted through urine.
[3]. 50% of the circulating glucagon is degraded in blood itself by enzymes such as serine and cysteine proteases.
Actions of Glucagon .
[1]. Actions of glucagon are antagonistic to those of insulin .
[2]. It increases the blood glucose level, peripheral utilization of lipids and the conversion of proteins into glucose.
1. On Carbohydrate Metabolism .
Glucagon increases the blood glucose level by:
1. Increasing glycogenolysis in liver and releasing glucose from the liver cells into the blood. Glucagon does not induce glycogenolysis in muscle
2. Increasing gluconeogenesis in liver by:
a. Activating the enzymes, which convert pyruvate into phosphoenol pyruvate
b. Increasing the transport of amino acids into the liver cells. The amino acids are utilized for glucose formation.
2. On Protein Metabolism .
[1]. Glucagon increases the transport of amino acids into liver cells.
[2]. The amino acids are utilized for gluconeogenesis.
3. On Fat Metabolism .
[1]. Glucagon shows lipolytic and ketogenic actions.
[2]. It increases lipolysis by increasing the release of free fatty acids from adipose tissue and making them available for peripheral utilization.
[3]. The lipolytic activity of glucagon, in turn promotes ketogenesis (formation of ketone bodies) in liver.
4. Other Actions of Glucagon .
1. Inhibits the secretion of gastric juice .
2. Increases the secretion of bile from liver.
Mode of Action of Glucagon .
[1]. On the target cells (mostly liver cells), glucagon combines with receptor and activates adenyl cyclase via G protein.
[2]. Adenyl cyclase causes the formation of cyclic adenosine monophosphate (AMP) which brings out the actions of glucagon.
[3]. Glucagon receptor is a peptide with a molecular weight of 62,000.
Regulation of Glucagon Secretion .
Secretion of glucagon is controlled mainly by glucose and amino acid levels in the blood.
1. Role of Blood Glucose Level .
[1]. Important factor that regulates the secretion of glucagon is the decrease in blood glucose level.
[2]. When blood glucose level decreases below 80 mg/dL of blood, α-cells of islets of Langerhans are stimulated and more glucagon is released.
[3]. 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. Role of Amino Acid Level in Blood .
[1]. Increase in amino acid level in blood stimulates the secretion of glucagon.
[2]. Glucagon, in turn converts the amino acids into glucose.
3. Role of Other Factors .
Factors which increase glucagon secretion:
1. Exercise .
2. Stress .
3. Gastrin .
4. Cholecystokinin (CCK) .
5. Cortisol.
Factors which inhibit glucagon secretion:
1. Somatostatin .
2. Insulin .
3. Free fatty acids .
4. Ketones.
Somatostatin .
Source of Secretion of Somatostatin .
Somatostatin is secreted from:
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 of Somatostatin .
[1]. Somatostatin is a polypeptide.
[2]. It is synthesized in two forms, namely somatostatin-14 (with 14 amino acids) and somatostatin-28 (with 28 amino acids). Both the forms have similar actions.
[3]. Half-life of somatostatin is 2 to 4 minutes.
Synthesis of Somatostatin .
[1]. Somatostatin is synthesized from the precursor prosomatostatin.
[2]. Prosomatostatin is converted mostly into somatostatin-14 in the D cells of islets in pancreas. However, in the intestine, large amount of somatostatin28 is produced from prosomatostatin.
Metabolism of Somatostatin .
Somatostatin is degraded in liver and kidney.
Actions of Somatostatin .
1. Somatostatin acts within islets of Langerhans and, inhibits β and α cells, i.e. 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, GIP and VIP
4. Hypothalamic somatostatin inhibits the secretion of GH and TSH from 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 .
Pancreatic Somatostatin .
[1]. Secretion of pancreatic somatostatin is stimulated by glucose, amino acids and CCK.
[2]. The tumor of D cells of islets of Langerhans causes hypersecretion of somatostatin.
[3]. It leads to hyperglycemia and other symptoms of diabetes mellitus.
Gastrointestinal Tract Somatostatin .
Secretion of somatostatin in GI tract is increased by the presence of chyme-containing glucose and proteins in stomach and small intestine.
Pancreatic Polypeptide .
Source of Secretion of Pancreatic Polypeptide .
[1]. Pancreatic polypeptide is secreted by F cells or PP cells in the islets of Langerhans of pancreas.
[2]. It is also found in small intestine.
Chemistry & Half-life of Pancreatic Polypeptide .
[1]. Pancreatic polypeptide is a polypeptide with 36 amino acids.
[2]. Its half-life is 5 minutes.
Synthesis of Pancreatic Polypeptide .
Pancreatic polypeptide is synthesized from preprohormone precursor called prepropancreatic polypeptide in the PP cells of islets.
Metabolism of Pancreatic Polypeptide .
Pancreatic polypeptide is degraded and removed from circulation mainly in kidney.
Actions of Pancreatic Polypeptide .
[1]. Exact physiological action of pancreatic polypeptide is not known.
[2]. 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 of Pancreatic Polypeptide .
Secretion of pancreatic polypeptide is stimulated by the presence of chyme containing more proteins in the small intestine.
Regulation of Blood Glucose level (Blood Glucose Level ) .
Normal Blood Glucose Level .
[1]. In normal persons, blood glucose level is controlled within a narrow range.
[2]. In the early morning after overnight fasting, the blood glucose level is low ranging between 70 and 110 mg/dL of blood.
[3]. Between first and second hour after meals (postprandial), the blood glucose level rises to 100 to 140 mg/dL.
[4]. Glucose level in blood is brought back to normal at the end of second hour after the meals.
[5]. Blood glucose regulating mechanism is operated through liver and muscle by the influence of the pancreatic hormones – insulin and glucagon.
[6]. Many other hormones are also involved in the regulation of blood glucose level.
[7]. Among all the hormones, insulin is the only hormone that reduces the blood glucose level and it is called the antidiabetogenic hormone.
[8]. The hormones which increase blood glucose level are called diabetogenic hormones or anti-insulin hormones.
Necessity of Regulation of Blood Glucose Level .
Regulation of blood glucose (sugar) 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 Liver in the Maintenance of Blood Glucose Level .
[1]. Liver serves as an important glucose buffer system.
[2]. When blood glucose level increases after a meal, the excess glucose is converted into glycogen and stored in liver.
[3]. Afterwards, when blood glucose level falls, the glycogen in liver is converted into glucose and released into the blood.
[4]. The storage of glycogen and release of glucose from liver are mainly regulated by insulin and glucagon.
Role of Insulin in the Maintenance of Blood Glucose Level .
Insulin decreases the blood glucose level and it is the only antidiabetic hormone available in the body .
Role of Glucagon in the maintenance of Blood Glucose level .
Glucagon increases the blood glucose level .
Role of Other Hormones in the Maintenance of Blood Glucose Level .
Other hormones which increase the blood glucose level are:
1. Growth hormone .
2. Thyroxine .
3. Cortisol .
4. Adrenaline .
[1]. Thus, liver helps to maintain the blood glucose level by storing glycogen when blood glucose level is high after meals; and by releasing glucose, when blood glucose level is low after 2 to 3 hours of food intake.
[2]. Insulin helps to control the blood glucose level, especially after meals, when it increases.
[3]. Glucagon and other hormones help to maintain the blood glucose level by raising it in between the meals .
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