Insulin Function and metabolism

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 Function and metabolism

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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