Zoology · Ch 10 — Applications of Biotechnology
Recombinant Human Insulin
Recombinant Human Insulin
Human insulin is a small protein hormone made by the beta cells of the pancreatic Islets of Langerhans. It consists of two short polypeptide chains — a 21-amino-acid A chain and a 30-amino-acid B chain — held together by disulphide (S–S) bridges, and its job is to let body cells take up glucose from the blood for energy. When insulin production fails, blood glucose stays chronically high, a condition called diabetes mellitus that is fatal if left untreated and needs a continuous supply of insulin to manage. For decades that supply came from the pancreases of slaughtered pigs and cows, but the small structural differences between animal and human insulin caused allergic reactions in a meaningful fraction of patients. Recombinant DNA technology solved this in the late 1970s by inserting the human insulin gene into E. coli plasmids: the bacteria are engineered to first make a single precursor chain, pre-pro-insulin, carrying a leader sequence and a connecting C-chain in addition to the A and B chains; the leader sequence is cleaved after translation and the C-chain is then excised, leaving the correctly folded, fully human two-chain insulin. This was the very first pharmaceutical product ever made by recombinant DNA techn …
What this figure shows. A flow diagram tracing recombinant human insulin manufacture end to end: the human insulin-producing gene is identified in a human pancreas cell; a bacterial plasmid is cut open with restriction enzymes; the human gene is spliced into the cut plasmid to form recombinant DNA; this recombinant plasmid is introduced into a bacterium; the transformed bacterium is grown and multiplied in a fermentation tank where it manufactures human insulin; the insulin is then extracted and purified from the culture. A separate inset shows the molecular detail: pre-pro-insulin (a single chain with a signal/leader peptide plus the A, B and C segments) is processed to pro-insulin, the leader peptide and the C-chain are excised, and the mature two-chain insulin (A chain and B cha …