BIOTECHNOLOGY - V. H. Herasymenko - 2006

Part II. Applied Biotechnologies

Chapter 12. HORMONES PRODUCTION BIOTECHNOLOGY

12.2. PRODUCTION OF INSULIN

Insulin is a hormone produced by the islets of Langerhans in the Pancreas that regulates Carbohydrate METABOLISM and maintains normal Blood sugar levels. A deficiency of this hormone in the body leads to Diabetes Mellitus, one of the most severe diseases. According to statistics, in 1985 over 80 million people worldwide suffered from this condition, which ranks third in prevalence after cardiovascular and oncological diseases.

Insulin is a small globular protein containing 51 amino acid residues, The sequence of which was determined by Sanger in 1955. It consists of two polypeptide chains, A and B (comprising 21 and 30 Amino Acids, respectively), linked together by two disulfide bridges. Insulin is synthesized on Ribosomes in the β-Cells of the pancreatic islets of Langerhans as a single-chain precursor, preproinsulin,

with a length of 109 amino acids. The first 23 amino acids serve as a signal for the insulin molecule to cross The Cell membrane. They are cleaved off to form proinsulin, which is 86 amino acid residues long. The proinsulin molecule folds in such a way that its initial and terminal segments come into close proximity, while the central part of the molecule is cleaved off by enzymatic action. The Role of this central segment is to ensure the correct relative orientation of the two insulin chains.