In this article we will discuss about Insulin. After reading this article you will learn about: 1. Meaning of Insulin 2. Structure of Insulin 3. Biosynthesis.
Meaning of Insulin:
Insulin is a type of protein hormone, which is synthesized in the β-cells of islets of Langerhans. The term insulin is derived from Latin word “Insula” means island. Banting and Best (1916) observed the role of insulin in glucose metabolism.
Structure of Insulin:
Insulin is a peptide hormone and its molecular weight is 5.7 Kdt. It is made up of two polypeptide chains α and β. Insulin is constituted by 51 amino acids, of which a-chain contains 21 amino acids and β-chain contains 30 amino acid residues. Besides the primary peptide bonds, the polypeptide chains are strengthened by disulphide bonds (-S-S-).
One intra -S-S- bond occurs in the a-chain in between 6 and 11 positions of cystine. Two inter -S-S- bonds are found in between a and p chain one in between 7th position of both the chains and other in between 20th position of α-chain and 19th position of β-chain (Fig. 6.1).
In different species of vertebrates, structure of insulin varies according to variation of amino acid residues. Variations occur at 8th, 9th and 10th position of a-chain and 30th position of β-chain.
Biosynthesis of Insulin:
The synthesis of insulin takes place in p-cells of islets of Langerhans.
It is a complex phenomenon and it occurs in following ways:
1. Transcription of code:
Genes on chromosome 11 coding for insulin and are transcribed to mRNA in the nucleus.
2. Translation of the code:
After moving to the cytoplasm, mRNA is translated by the polysome attach to GER. Polypeptide synthesis is initiated with the formation of N-terminal signal peptide (leading sequence) which penetrates through the membrane of GER.
3. Synthesis of preproinsulin:
Further elongation directs the polypeptide chain into the lumen of GER, resulting in the formation of preproinsulin. It is constituted by 109 amino acid residues and mol. wt. is 11.5 kdt.
4. Separation of signal sequence:
In the lumen of GER, N-terminal signal peptide is hydrolysed away by signal peptidase. Thus signal peptide is cleaved and pro- insulin is formed in the cysternal space of GER. Pro-insulin consists of 86 amino acid residues and its mol. wt. is about 9 kd. Pro-insulin has disulphide bonds.
5. Transfer of pro-insulin:
Pro-insulin is transported from GER to the Golgi complex.
6. Splitting of pro-insulin:
In Golgi cisternae pro-insulin is hydrolysed by trypsin like peptidase to yield a 53 amino acid insulin precursor and pro-c-peptide has 33 amino acids.
Under condition of excessive stimulation pro-insulin is secreted by vesicular exocytosis along with the insulin from p-cells (Fig. 6.2).
7. Formation of insulin:
In the Golgi complex about 95% of the pro-insulin is converted to active insulin. Enzyme carboxylase peptidase hydropses c-terminal peptide bonds in the pro-c- peptide and the insulin precursor to release 2-c-terminal basic amino acids from each. Two molecules of Arg. are driven out from the insulin precursor and lead to the formation of active insulin (consists of 51 amino acids).
From pro-c-peptide two amino acids Lys and Arg are separate out and leads to the formation of connective peptide or c-pep- tide (consists of 31 amino acids). Insulin and c-peptide are present in secretory granules of Golgi complex. In some species, insulin is combined with Zn within P-cells. After stimulation insulin is secreted by exocytosis (Fig. 6.3).
Transport of insulin:
Insulin is directly diffused within the blood sinusoids of the islets and is transported to the target organ.
Catabolism of insulin:
After biochemical reaction, insulin is degraded within the liver, kidney, skeletal muscles and placenta in presence of enzyme insulinase.
Control of secretion:
Insulin synthesis and secretion is controlled by following factors:
1. Carbohydrate meal:
Intake of carbohydrate rich food leads to raise the blood glucose which is signal for increased insulin secretion.
2. Amino acids:
Ingestion of protein causes an increase in plasma amino acids level. Elevated plasma arginine is particularly potent stimulus for insulin secretion.
3. Gastrointestinal hormone:
Intestinal hormones (GIP & VIP) secretion stimulates the insulin synthesis and secretion.
4. Epinephrine:
The synthesis and release of insulin are degraded by negative feedback mechanism of epinephrine in stress condition.
5. Glucagon:
Low blood sugar level stimulates the secretion of glucagon for glycogenesis, which in-turn inhibits the synthesis of insulin (Fig. 6.4).
6. Somatostatin:
This hormone is secreted from D-cells of pancreatic islets and regulates the secretion α and β-cells.