Insulin
...discovery of insulin. Although the discovery is appropriately attributed to Banting and Best, others provided important observations and techniques that made it possible. In 1869, a German medical student, Paul Langerhans, noted that the pancreas contains two distinct groups of cellsthe acinar cells, which secrete digestive enzymes, and cells that are clustered in islands, or islets, which he suggested served a second function. Direct evidence for this function came in 1889, when Minkowski and von Mering showed that pancreatectomized dogs exhibit a syndrome similar to diabetes mellitus in humans.
Chemistry.Insulin was purified and crystallized by Abel within a few years of its discovery. Sanger established the amino acid sequence of insulin in 1960, the protein was synthesized in 1963, and Hodgkin and coworkers elucidated insulin's three-dimensional structure in 1972. Insulin was the hormone for which Yalow and Berson first developed the radioimmunoassay
The (or B) cells of pancreatic islets synthesize insulin from a single-chain precursor of 110 amino acids termed preproinsulin. After translocation through the membrane of the rough endoplasmic reticulum, the 24-amino-acid N-terminal signal peptide of preproinsulin is cleaved rapidly to form proinsulin Thereafter, proinsulin folds, and the disulfide bonds form. During conversion of human proinsulin to insulin, four basic amino acids and the remaining connector or C peptide are removed by proteolysis. This gives rise to the A and B peptide chains of the insulin molecule, which contains one intrasubunit and two intersubunit disulfide bonds. The A chain usually is composed of 21 amino acid residues, and the B chain has 30; the molecular mass is thus about 5734 daltons. Although the amino acid sequence of insulin has been highly conserved in evolution, there are significant variations that account for...
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