Insulin
Insulin is a hormone, which contriutes to cell signalling. Its main function is the regulation of blood sugar levels, by causing the liver and muscles to increase uptake of glucose [1]. Insulin is produced from a single gene which codes for the peptide proinsulin; a precursor molecule. Mutations in this gene can result in a faulty protein; causing type 1 diabetes or a possible predisposition to type 2 diabetes [2][3].
Insulin regulates the blood glucose levels in different ways. It enhances the glucose transport at a cellular level by stimulation of the glucose transporter (GLUT) family.
Insulin also has an effect on gene expression which is up or down regulated in the homeostasis process to maintain the optimum blood glucose levels.
Insulin is released by the beta-cells (Islets of Langerhans) of the pancreas.
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History
Insulin was first discovered in 1921 by Dr Frederick Banting and Charles Best after removing the pancreas from dogs and cattle[4]. Frederick Sanger's pioneering research led him to discover the amino acid sequence of the insulin in 1953 [5].
Insulin stimulates glycogen synthesis
When blood sugar levels are high, insulin binds to a tyrosine kinase receptor. Binding of insulin triggers a phosphorylation cascade, preventing phosphorylation of glycogen synthase as this inactivates it's activity [6].
Insulin acts antagonistically to the hormone glucagon, which acts on glycogen storage in response to low blood sugar levels [7]. This serves as an effective homeostasis mechanism.
Origin of structure
Insulin (a globular protein) is extracted and purified by crystallisation from the beta cells of Langerhands of pancreas in pork and beef. It is made by using E. coli in recombinant DNA technology (biosynthetically) or enzymatic modification of porcine material (semisynthetically) [8].
Forming the structure of Insulin
Insulin has two peptide chains, named a and b which are linked together by disulphide bonds between each of the two chains. Proinsulin is the molecule that insulin is synthesised from, unlike insulin it contains three peptide chains (a, b and c). Proinsulin folds to the correct shape through the formation of the disulphide bonds between the a and b peptide chains and then the peptide chain, c, located between the a and the b chains is removed in order to complete the structure of insulin.
Physical properties
The physical property of insulin substance is white in colour and it is in the form of white crystalline powder because it is purified by crystallisation, hence 'crystalline'. It is soluble in water and dilute solution of mineral acids and insoluble in alcohol.chloroform and ether [9].
Using recombinant DNA technology to produce active insulin molecules
We can use recombinant DNA technology to produce active insulin molecules using bacteria or yeast cells. Insulin is made from 2 polypeptide chains A and B which are linked by disulphide bonds. Insulin is taken from the pancreas and the chains are separated. The introns are then removed from the chains to produce proinsulin and the proinsulin is then inserted into plasmids. Many plasmids containing the insulin are then inserted into the host cell. As the cells reproduce the human insulin gene is also reproduced in the new cells. The insulin proteins can then be collected and purified so it can be used. This insulin can then used by people with diabetes.[10] Insulin is made this way as it is a lot more likely for the body to accept the insulin and not recognise it as a foreign body- this is because it is identical to the insulin being produced by the human pancreas; unlike using insulin from animals(pigs).
References
- ↑ http://www.ncbi.nlm.nih.gov/omim/176730
- ↑ http://www.ncbi.nlm.nih.gov/omim/176730
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/20806184
- ↑ Nobelprize.org, "The Discovery of Insulin" (2013). http://www.nobelprize.org/educational/medicine/insulin/discovery-insulin.html (last accessed 27.11.13)
- ↑ Lubert Stryer (1995). Biochemistry. 4th ed. New York : W.H. Freeman . 25.
- ↑ Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: WH Freeman.fckLR
- ↑ Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: WH Freeman.fckLR
- ↑ http://www.inchem.org/documents/pims/pharm/insulin.htm#SectionTitle:3.2 Chemical structure
- ↑ http://www.inchem.org/documents/pims/pharm/insulin.htm#SectionTitle:3.2 Chemical structure
- ↑ Griffiths AJF, Gelbart WM, Miller JH, et al. Modern Genetic Analysis. New York: W. H. Freeman; 1999. Expressing Eukaryotic Genes in Bacteria.
