SMRITI SINGH
UNIVERSITY DEPT. OF ZOOLOGY
S.K.M.UNIVERSITY
DUMKA-814110
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T.S OF PANCREAS
PHYSIOLOGICAL ROLE OF HORMONES
1.GLUCAGON
·
Glucagon
is also called the hyperglycemic hormone
·
Most
of the actions of glucagon are achieved by activation of adenylyl cyclase in
hepatic cell membrane
·
The
binding of glucagon to hepatic receptors results in activation of adenylyl
cyclase and generation of the second messenger cyclic AMP, which in turn
activates protein kinase, leading to phosphorylation that results in the
activation or deactivation of a number of enzymes.
·
Glucagon
raises blood glucose level up to normal by
stimulating Glycogenolysis (hydrolysis of glycogen in liver,
releasing glucose level).
·
Glucagon
also promotes Glyconeogenesis (formation of glucose from
non-carbohydrate organic compound). Glucagon increase the transport of AA
into liver cells, where after deaminate the AA (keto group) are
converted into glucose.
·
Glucagon
also enhances lipolysis in adipose tissue, releasing fatty acids and glycerol
which also can be converted into glucose.
Effects on glucose metabolism
·
Glucagon
promotes hyperglycemia
·
Greatly
enhance the availability of glucose to the organs of the body
·
Glucagon
stimulates glycogenolysis:
·
Glucagon
has immediate and pronounced effects on the liver to increase glycogenolysis
and the release of glucose into the blood
·
This
effect is achieved through activation of liver phosphorylase and simultaneous
inhibition of glycogen synthase
·
Glucagon
stimulates gluconeogenesis:
·
Glucagon
increases the hepatic extraction of amino acids from the plasma and increases
the activities of key glucaneogenic enzymes
·
Consequently,
glucagon has delayed actions to promote glucose output by the liver
Other effects of glucagon
·
Occurs
only when its concentration rises well above the maximum normally found in the
blood
·
Activate
adipose cell lipase, making increased quantities of fatty acids available to
the energy systems of the body
·
Glucagon
also inhibits the storage of triglycerides in the liver, which prevents the
liver from removing fatty acids from the blood
·
Enhances
the strength of the heart
·
Increases
blood flow in some tissues, especially the kidneys
·
Enhance
bile secretion
·
Inhibits
gastric acid secretion
Regulation of glucagon secretion
·
Increased
blood glucose inhibits glucagon secretion
·
Increased
blood amino acids stimulate glucagon secretion
·
Somatostatin
inhibits glucagon and insulin secretion
2. INSULIN
It reduces blood glucose level and making it the
normal condition. It increases the membrane permeability of its target cells
such as muscles cell, liver cell, adipose cell etc.
·
Glucose in presence of insulin,
easily enter the cell from body fluid i.e; blood.
·
Insulin is a hormone associated with
energy abundance
·
When there is great abundance of
energy-giving foods in the diet, especially excess amounts of carbohydrates.
Insulin is secreted in great quantity
·
Insulin plays an important role in
storing the excess energy.
·
In the case of excess carbohydrates,
it causes them to be stored as glycogen mainly in the liver and muscles.
·
Excess carbohydrates is also
converted under the stimulus of insulin into fats and stored in the adipose
tissue.
·
Insulin has a direct effect in
promoting amino acid uptake by cells and conversion of these amino acids into
protein.
·
In addition, it inhibits the
breakdown of the proteins that are already in the cells.
Actions of insulin
·
To initiate its effects on target
cells, insulin first binds with and activates a membrane receptor protein
·
The insulin receptor is a tetramer
made up of two α-subunits that lie outside of the cell membrane and
two β-subunits that penetrate the cell membrane and
protrude into the cytoplasm
·
When insulin binds with the α- subunits
on the outside of the cell, portions of the β-subunits
protruding into the cell become auto phosphorylated.
·
Thus, the insulin receptor is an
example of an enzyme-linked receptor
·
Autophosphorylation of the β-subunits
of the receptor activates a local tyrosine kinase, which in turn causes
phosphorylation of multiple other intracellular enzymes including a group
called insulin-receptor subunits (IRS)
·
The net effect is to activate some of
these enzymes while inactivating others.
·
In this way, insulin directs the
intracellular metabolic machinery to produce the desired effects on
carbohydrate, fat, and protein metabolism.
Effect on carbohydrate metabolism
·
Immediately after a high-carbohydrate
meal, glucose that is absorbed into the blood causes rapid secretion of insulin
·
Insulin causes rapid uptake, storage
and use of glucose by almost all tissues of the body, but especially by the
muscles, adipose tissue, and liver.
·
In muscle, insulin promotes the
uptake and metabolism of glucose
·
Mostly muscle tissue depends not on
glucose for its energy but on fatty acids, because normal resting muscle
membrane is only slightly permeable to glucose, except when the muscle fibre is
stimulated by insulin.
·
Under two conditions the muscles do
use large amounts of glucose.
1. During moderate or heavy exercise, because
exercising muscle fibres become more permeable to glucose even in the absence
of insulin.
2. during few hours after a meal: At this time the
blood glucose concentration is high and the pancreas is secreting large
quantities of insulin. The extra insulin causes rapid transport of glucose into
the muscle cells.
·
Abundant glucose transported into the
muscle cells is stored in the full form of muscle glycogen
·
In the liver, insulin promotes
glucose uptake and storage and use
·
Insulin causes most of the glucose
absorbed after a meal to be stored almost immediately in the liver in the form
of glycogen.
The mechanism of glucose uptake and storage in the liver:
1. Insulin
inactivates liver phosphorylase, which normally causes liver glycogen to split
into glucose.
2. Insulin
causes enhanced uptake of glucose from blood by liver by increasing the
activity of the enzyme glucokinase, causes the initial phosphorylation of
glucose after it diffuses into liver
3. Insulin
also increases the activities of the enzymes that promote glycogen synthesis,
glycogen synthase
Glucose is released from the liver between meals
When the blood glucose level
begins to fall to a low level between meals, several events cause the liver to
release glucose back into the circulating blood:
1. The
decreasing blood glucose causes the pancreas to decrease its insulin secretion.
2. The
lack of insulin then reverses all the effects for glycogen storage
3. The
lack of insulin activates the enzyme phosphorylase, causes the splitting of
glycogen into glucose phosphate.
4. The
enzyme glucose phosphatase, now becomes activated by the insulin lack and
causes the phosphate radical to split away from the glucose
·
Thus, the liver removes glucose from
the blood when it is present in excess after a meal and returns it to the blood
when the blood glucose concentration falls between meals
·
Insulin promotes conversion of excess
glucose into fatty acids and inhibits gluconeogenesis in liver
·
When the quantity of glucose entering
the liver cells is more, insulin promotes the conversion of all this excess
glucose into fatty acids.
·
These packaged as triglycerides in
VLDL and transported by blood to the adipose tissue and deposited as fat.
·
Insulin also inhibits
gluconeogenesis.
·
Lack of effect of insulin on glucose
uptake and usage by the brain
·
Insulin has little effect on uptake
or use of glucose in brain
·
Instead, the brain cells are
permeable to glucose
·
The brain cells are also quite
different from most other cells of the body in that they normally use only
glucose for energy and can use other energy substrates, such as fats, only with
difficulty.
·
It is essential that the blood
glucose level always be maintained above a critical level
·
When the blood glucose falls too low,
symptoms of hypoglycaemic shock develop, characterized by progressive nervous
irritability that leads to fainting, seizures and even coma.
·
Insulin increases glucose transport
into and glucose usage by most other cells of the body
·
The transport of glucose into adipose
cells mainly provides substrate for the glycerol portion of the fat molecule
·
Therefore, in this indirect way,
insulin promotes deposition of fat in these cells.
Effect of insulin on fat metabolism
·
Insulin promotes fat synthesis and
storage
·
Insulin has several effects that lead
to fat storage in adipose tissue.
·
Insulin increases the utilization of
glucose by body
·
Insulin promotes fatty acid
synthesis, in liver cells
·
Fatty acids are then transported from
the liver by way of the blood lipoproteins to the adipose cells to be stored
Role of insulin in storage of fat in the adipose cells
Insulin has two other essential
effects that are required for fat storage in adipose cells:
1. Insulin
inhibits the action of hormone-sensitive lipase. This is the enzyme that causes
hydrolysis of the triglycerides already stored in the fat cells.
2. Insulin
promotes glucose transport through the cell membrane into the fat cells. Some
of this glucose is then used to synthesize minute amounts of fatty acids, but
forms large quantities of a glycerol phosphate. This substrate supplies the glycerol
that combines with fatty acids to form the triglycerides that are the storage
form of fat
·
Insulin deficiency increases plasma
cholesterol and phospholipid concentrations
·
The excess of fatty acids in the
plasma associated with insulin deficiency also promotes liver conversion of
some of the fatty acids into phospholipids and cholesterol, two of the major
products of fat metabolism.
·
These two substances, along with
excess triglycerides into the blood in the lipoproteins increase
·
This high lipid
concentration-especially the high concentration of cholesterol- promotes the
development of antherosclerosis in people with serious diabetes.
·
Excess usage of fats during insulin
lack causes ketosis and acidosis
·
Insulin lack also causes excessive amounts
of acetoacetic acid to be formed in the liver cells.
·
At the same time, the absence of
insulin also depresses the utilization of acetoacetic acid in the peripheral
tissues.
·
Thus, so much acetoacetic acid is
released from the liver
Some of the acetoacetic acid is also converted into b-hydroxybutyric
acid and acetone.
·
These two substances, along with the
acetoacetic acid, are called ketone bodies, and their presence in large
quantities in the body fluids is called ketosis.
·
In severe diabetes the acetoacetic
acid and b-hydroxybutyric acid can cause severe
Effect of insulin on protein metabolism and on growth
Insulin promotes protein synthesis and storage
During the few hours after a meal protein are also stored in the tissues
by insulin
1. Insulin
stimulates transport of many of amino acids into the cells, e.g; valine, leucine,
isoleucine, tyrosine and phenylalanine.
2. Insulin
increases the translation of mRNA, thus forming new proteins
3. Over
a longer period of time, insulin also increases the rate of transcription of
selected DNA, forming increased quantities of RNA and still more protein
synthesis.
4. Insulin
inhibits the catabolism of proteins
5. In
the liver, insulin depresses the rate of gluconeogenesis, this suppression of
gluconeogenesis conserves the amino acids in the protein stores of the body.
·
In summary, insulin promotes protein
formation and prevents the degradation of proteins
·
Insulin lack causes protein depletion
and increased plasma amino acids
·
The resulting protein wasting is one
of the most serious of all effects of severe diabetes mellitus.
·
It can lead to extreme weakness as
well as many
Factors and conditions that increase or decrease insulin secretion
Increase insulin secretion
|
Decrease insulin secretion
|
1. Increased blood
glucose
|
1.Decreased
blood glucose
|
2. Increased blood
free fatty acids
|
2.Fasting
|
3.
Increased blood amino acids
|
3.somatostatin
|
4.
Gastrointestinal hormones (gastrin, cholecystokinin,
secretin, gastric inhibitory peptide)
|
4.α-adrenergic activity
|
5.
Glucagon, growth hormone, cortisol
|
5.Leptin
|
6.
Parasympathetic stimulation: acetylcholine
|
|
7.
β-adrenergic stimulation
|
|
8.
insulin resistance: obesity
|
|
9.
sulfonylurea drugs (glyburide, tolbutamide)
|
Hormonal disorders
* Under secretion of insulin leads to
rise in blood glucose level which decreases the cell permeability for glucose.
* It causes a disease known as Diabetes
mellitus.
* Normal blood glucose level should be
80-100 mg/100 ml of blood.
* The hypo secretion of insulin raises
this level leading to Hyperglycemia and a person suffering from this disease
has a plenty of sugar in blood as well as in urine.
* Sometimes hyper secretion of insulin
lowers the blood glucose level and caused Hypoglycaemia. In this stage person
has to face a convolution stage.
* Over secretion of Glucagon level
known as Hyperglycaemia while under secretion leads to Hypoglycaemia.
