Insulin

INSULIN

Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct. It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger. Insulin is a two chain polypeptide having 51 amino acids and MW about 6000. The Achain has 21 while Bchain has 30 amino acids. There are minor differences between human, pork and beef insulins:

Thus, pork insulin is more homologous to human insulin than is beef insulin. The A and B chains are held together by two disulfide bonds.

Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which 24 AAs are first removed to produce Proinsulin (Fig. 19.1). The connecting or ‘C’ peptide (35 AA) is split off by proteolysis in Golgi apparatus; both insulin and C peptide are stored in granules within the cell. The C peptide is secreted in the blood along with insulin.

Assay

Insulin is bioassayed by measuring blood sugar depression in rabbits (1 U reduces blood glucose of a fasting rabbit to 45 mg/dl) or by its potency to induce hypoglycaemic convulsions in mice. 1 mg of the International Standard of insulin = 28 units. With the availability of pure preparations, it can now be assayed chemically also. Plasma insulin can be measured by radioimmunoassay or enzyme immunoassay.