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.
INSULIN
SOURCE OF SECRETION
Insulin is
secreted by B cells or the β-cells in the islets of Langerhans
of pancreas.
CHEMISTRY AND
HALF-LIFE
Insulin is
a polypeptide with 51 amino acids and a molecular weight of 5,808. 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 β-chain contains 30 amino acids. The biological half-life
of insulin is 5 minutes.
PLASMA LEVEL
Basal
level of insulin in plasma is 10 μU/mL.
SYNTHESIS
Synthesis of insulin occurs
in the rough endoplasmic reticulum of β-cells in islets of
Langerhans. It is synthesized as preproinsulin, that gives rise to proinsulin. Proin
sulin is converted into insulin and C peptide through a series of peptic cleavages.
C peptide is a connecting peptide that connects α and β
chains. At the time of secretion, C peptide is detached.
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.
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.
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
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 by the following actions:
i. Facilitating the transport
of amino acids into the cell from blood, by increasing the
permeability of
cell membrane for amino
acids
ii.
Accelerating protein synthesis by influencing the transcription of DNA
and by increasing the
translation of mRNA
iii. Preventing protein
catabolism by decreasing the activity of cellular enzymes
which act on
proteins
iv. Preventing 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.
Actions of insulin on fat
metabolism are:
i. 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:
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
Along with
growth hormone, insulin promotes growth of body by its anabolic action on
proteins. It enhances the 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.
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 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). 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. 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. 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
Insulin promotes the 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.
iii. Promotes storage
of glucose – glycogenesis
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. 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
Insulin
prevents glycogenolysis, i.e. the breakdown of glycogen into glucose in
muscle and liver.
v. Inhibits
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 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
On Protein Metabolism
Insulin facilitates the
synthesis and storage of proteins and inhibits the cellular utilization of
proteins by the following actions:
i. Facilitating the transport
of amino acids into the cell from blood, by increasing the
permeability of
cell membrane for amino
acids
ii.
Accelerating protein synthesis by influencing the transcription of DNA
and by increasing the
translation of mRNA
iii. Preventing protein
catabolism by decreasing the activity of cellular enzymes
which act on
proteins
iv. Preventing 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.
Actions of insulin on fat
metabolism are:
i. 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:
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
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 increasing the glucose
utilization by the tissues.
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