PMC9763182_01
(A) Amino acid sequence and structure of human insulin. (B) Three-dimensional structure of insulin. At high concentration, two insulin monomers self-associate to form a dimer, and three dimers (with two zinc ions, shown as grey sphere in 3D hexamer image) can self-associate into hexamers for efficient storage before exocytosis (The blue arrows in the monomer and dimer represent a beta sheet:a secondary structure element in a protein in which amino acids are arranged in an elongated fashion). Adapted from figure 2 in Hirsch et al, distributed under the terms of the Creative Commons CC BY license, using illustrations of crystal structures (PDB ID 6S34 and PDB ID 1MSO) determined and provided by Eva Johansson, Novo Nordisk.
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F1
Insulin was the first protein to be fully sequenced (as a 21-amino acid A-chain linked to a 30-amino acid B-chain by two disulfide bonds; figure 1), by Frederick Sanger in 1951, who received the Nobel Prize in Chemistry for this research.
Selected 20th century milestones, following its initial discovery in 1921, in further understanding of the insulin molecule and its physiology (green panels), and of diabetes (blue panels) and its treatment (grey panels). AGEs, advanced glycation end products; DCCT, Diabetes Control and Complications Trial; HbA1c, glycated haemoglobin; PD, pharmacodynamic; T1D, type 1 diabetes; T2D, type 2 diabetes.
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F2
Several other key discoveries in diabetes and insulin are summarised in figure 2. 