Insulin & Glucagon Hormones

2019.2020

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2020-2019
Dr: Asma’a Al-Henhena
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 Introduction
Ductless Glands
1. Pituitary
2. Thyroid
3. Parathyroid
4. pancreas
5. Suprarenal
6. Thymus
7. Ovary
8. Tests
9. Others (tissues, cells)

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 Functional Anatomy And Nerve Supply Of Pancreas
Pancreas is a dual organ having two functions, namely:
1. Endocrine function is concerned with the production of hormones
(producing insulin and glucagon).

2. Exocrine function is concerned

with the secretion of digestive
juice called pancreatic juice.

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 Endocrine function
• Islets Of Langerhans
Endocrine function of pancreas is performed by the islets of Langerhans. Human
pancreas contains about 1 to 2 million islets.
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.

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 Insulin
• Source Of Secretion , half-life & Basal level
Insulin is secreted by B cells or the β-cells in the islets of
Langerhans of pancreas. The biological half-life of insulin
is 5 minutes. Basal level of insulin in plasma is 10 µU/mL.

• Metabolism
Binding of insulin to insulin receptor is essential for its removal from circulation and
degradation. Insulin is degraded in liver and kidney by a cellular enzyme called insulin
protease or insulin-degrading enzyme.

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 Actions Of Insulin
Insulin is the important hormone that is concerned with the regulation of carbohydrate
metabolism and blood glucose level.
It is also concerned with the metabolism
of proteins and fats.

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1. On Carbohydrate Metabolism
Insulin is the only anti-diabetic hormone secreted in the body,
i.e. it is the only hormone in the body that reduces blood
glucose level. Insulin reduces the blood glucose level by its
following actions on carbohydrate metabolism:

i. Increases transport and uptake of glucose by the cells

Insulin facilitates the transport of glucose from blood into the cells by increasing
the permeability of cell membrane to glucose. 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.
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 1. On Carbohydrate Metabolism
• Insulin also increases the number of glucose transporters, especially GLUT 4 in the cell
membrane. It is present in large numbers in muscle fibers and adipose cells.
• The advantage of GLUT4 is that it
transports glucose at a faster rate.
ii. Promotes peripheral utilization of glucose
In presence of insulin, glucose which enters
the cell is oxidized immediately. The rate of
utilization depends upon the intake of glucose.

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iii. Promotes storage of glucose – glycogenesis
Insulin promotes the rapid conversion of glucose into glycogen (glycogenesis), which is
stored in two organs in the form of glycogen the muscle and liver. Insulin activates the
enzymes which are necessary for glycogenesis. In liver, when glycogen content increases
beyond its storing capacity, insulin causes conversion of glucose into fatty acids.

iv. Inhibits glycogenolysis

i.e. Insulin prevents the breakdown of glycogen into glucose in muscle
and liver.
v. Inhibits gluconeogenesis
i.e. Insulin prevents 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.
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Thus, insulin decreases the blood glucose level by:
i. Facilitating transport and uptake of glucose by the cells
ii. Increasing the peripheral utilization of glucose
iii. Increasing the storage of glucose by converting
it into glycogen in liver and muscle
iv. Inhibiting glycogenolysis
v. Inhibiting gluconeogenesis.

2. On Protein Metabolism
Insulin facilitates the synthesis and storage of proteins and inhibits the cellular
utilization of proteins. Thus, insulin is responsible for the conservation and storage of
proteins in the body.
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2020-2019
 3. On Fat Metabolism
• Insulin stimulates the synthesis of fat. It also increases the storage of fat in the adipose
tissue by inhibiting the enzymes which degrade the 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:
a. Glucose into fatty acids
b. Fatty acids into triglycerides.
4. On Growth
Along with growth hormone, insulin promotes growth of body by its anabolic action on
proteins. It enhances the transport of amino acids into the cell and synthesis of proteins
in the cells. It also has the protein-sparing effect, i.e. it causes conservation of proteins
by
2020increasing
-2019 the glucose utilization by Dr.the tissues.
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 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 blood glucose level is normal (80 to 100 mg/dL), the rate of insulin secretion
is low (up to 10 µU/minute).
• When blood glucose level increases between 100 and 120 mg/dL, the rate of insulin
secretion rises rapidly to 100 µU/minute.
• When blood glucose level rises above 200 mg/dL, the rate of insulin secretion also
rises very rapidly up to 400 µU/minute.

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 Biphasic effect of glucose
Action of blood glucose on insulin secretion is biphasic.
i. Initially, when blood glucose level increases after a meal, the
release of insulin into blood increases rapidly.
ii. Within few minutes, concentration of
insulin in plasma increases up to 100
µU/mL from the basal level of 10 µU/mL.
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.
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2020-2019 Dr. Asma’a Alhenhena
 iii. After 15 to 20 minutes, the insulin secretion rises once again. This time it rises slowly
but steadily. It reaches the maximum between 2 and 2½ hours. The prolonged increase
in insulin release is due to the formation of new insulin molecules continuously from
pancreas
2. Role of Proteins
• Excess amino acids in blood also stimulate insulin secretion. Without any increase in
blood glucose level, the amino acids alone can cause a slight increase in insulin secretion.
• 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.
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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 Diabetogenic hormones like glucagon, growth hormone

and cortisol also stimulate insulin secretion, indirectly

6. Role of Autonomic Nerves

Stimulation of parasympathetic nerve to the
pancreas (right vagus) increases insulin secretion.
Chemical neurotransmitter involved is acetylcholine.
Stimulation of sympathetic nerves inhibits the
secretion of insulin and the neurotransmitter is
noradrenaline.

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 Glucagon
 Source Of Secretion
Glucagon is secreted from A cells or α-cells in the islets of Langerhans of pancreas.
It is also secreted from A cells of stomach and L cells of intestine.
 Metabolism About 30% of glucagon is degraded in liver and 20% in kidney. The
cleaved glucagon fragments are excreted through urine. 50% of the circulating
glucagon is degraded in 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 glucose level,
peripheral utilization of lipids and the
conversion of proteins into glucose.

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 Actions Of Glucagon
1.On Carbohydrate
Metabolism Glucagon increases the blood glucose level by:
i. Increasing glycogenolysis in liver and releasing glucose from the liver cells into the blood.
ii. 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.

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2. On Protein Metabolism
Glucagon increases the 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 liver.
4. Other Actions Glucagon:
i. Inhibits the secretion of gastric juice
ii. Increases the secretion of bile from liver.

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 Mode Of Action Of Glucagon

• On the target cells (mostly liver cells), glucagon

combines with peptide receptor and activates
adenyl cyclase via G protein.
• Adenyl cyclase causes the formation of cyclic
adenosine monophosphate (AMP) which brings
out the actions of glucagon.

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 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 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.
Glucagon, in turn increases the blood glucose level.

2. Role of Amino Acid Level in Blood

Increase in amino acid level in blood stimulates the secretion of glucagon.
Glucagon, in turn converts the amino acids into glucose.

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3. Role of Other Factors which increase glucagon secretion:
i. Exercise iv. Cholecystokinin (CCK)
ii. Stress v. Cortisol.
iii. Gastrin

4. Factors which inhibit glucagon secretion:

i. Somatostatin
ii. Insulin
iii. Free fatty acids
iv. Ketones.

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 Somatostatin
 Source Of Secretion
Somatostatin is secreted from:
1. Hypothalamus
2. D cells (δ-cells) in islets of Langerhans of pancreas
3. cells in stomach and upper part of 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 the forms
have similar actions. Half-life of somatostatin is 2 to 4 minutes.
 Synthesis
Somatostatin-14 in the D cells of islets in pancreas. However, in the intestine, large
amount of somatostatin28 is produced.
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 Metabolism
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).

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

 Regulation Of Secretion Of Somatostatin

Pancreatic Somatostatin Secretion of pancreatic somatostatin is stimulated by
glucose, amino acids and CCK. The tumor of D cells of islets of Langerhans causes
hypersecretion of somatostatin. 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.

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 Regulation Of Blood Glucose Level (Blood Glucose Level)
 Normal Blood Glucose Level
• In normal persons, blood glucose level
is controlled within a narrow range. In
the early morning after overnight
fasting, the blood glucose level is low
ranging between 70 and 110 mg/dL of
blood.

• Between first and second hour after

meals (postprandial), the blood glucose
level rises to 100 to 140 mg/dL.
• Glucose level in blood is brought back to normal at the end of second hour after the meals.
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• Blood glucose regulating mechanism is operated through liver and muscle by the
influence of the pancreatic hormones – insulin and glucagon.
• Many other hormones are also involved in the regulation of blood glucose level. Among
all the hormones, insulin is the only hormone that reduces the blood glucose level and
it is called the antidiabetogenic hormone. The hormones which increase blood glucose
level are called diabetogenic hormones or anti-insulin hormones.

 Because blood glucose levels are allowed to deviate from the set point by about 20%
before any corrective mechanism is activated, glucagon and insulin can never both
be produced at the same time.

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 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

• Liver serves as an important glucose buffer system. When blood glucose level
increases after a meal, the excess glucose is converted into glycogen and stored in
liver.
• Afterwards, when blood glucose level falls, the glycogen in liver is converted into
glucose and released into the blood.
• The storage of glycogen and release of glucose from liver are mainly regulated by
insulin and glucagon.
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 Applied Physiology
Diabetes Mellitus
Classification of Diabetes Mellitus There are several forms
of diabetes mellitus, which occur due to different causes.
• Diabetes may be primary or secondary. Primary
diabetes is unrelated to another disease. Secondary
diabetes occurs due to damage or disease of pancreas
by another disease or factor.

• Recent classification divides primary diabetes

mellitus into two types, Type I and Type II.

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