Editing Insulin (section)

== Structure ==
{{See also|Insulin/IGF/Relaxin family|Insulin and its analog structure}}

[[Image:InsulinMonomer.jpg|250px|thumb|'''The structure of insulin.''' The left side is a space-filling model of the insulin monomer, believed to be biologically active. [[Carbon]] is green, [[hydrogen]] white, [[oxygen]] red, and [[nitrogen]] blue. On the right side is a [[ribbon diagram]] of the insulin hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulfide bonds, and magenta spheres are zinc ions.]]

Contrary to an initial belief that hormones would be generally small chemical molecules, as the first peptide hormone known of its structure, insulin was found to be quite large.<ref name=":0" /> A single protein (monomer) of human insulin is composed of 51 [[amino acid]]s, and has a [[molecular mass]] of 5808 [[Dalton (unit)|Da]]. The [[molecular formula]] of human insulin is C<sub>257</sub>H<sub>383</sub>N<sub>65</sub>O<sub>77</sub>S<sub>6</sub>.<ref>{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/16129672|title=Insulin human|publisher=[[PubChem]]|access-date=26 February 2019}}</ref> It is a combination of two peptide chains ([[protein dimer|dimer]]) named an A-chain and a B-chain, which are linked together by two [[disulfide bond]]s. The A-chain is composed of 21 amino acids, while the B-chain consists of 30 residues. The linking (interchain) disulfide bonds are formed at cysteine residues between the positions A7-B7 and A20-B19. There is an additional (intrachain) disulfide bond within the A-chain between cysteine residues at positions A6 and A11. The A-chain exhibits two α-helical regions at A1-A8 and A12-A19 which are antiparallel; while the B chain has a central α -helix (covering residues B9-B19) flanked by the disulfide bond on either sides and two β-sheets (covering B7-B10 and B20-B23).<ref name=":0" /><ref name=":1">{{cite journal | vauthors = Fu Z, Gilbert ER, Liu D | title = Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes | journal = Current Diabetes Reviews | volume = 9 | issue = 1 | pages = 25–53 | date = January 2013 | pmid = 22974359 | pmc = 3934755 | doi = 10.2174/157339913804143225 }}</ref>

The amino acid sequence of insulin is [[conserved sequence|strongly conserved]] and varies only slightly between species. [[Cow|Bovine]] insulin differs from human in only three [[amino acid]] residues, and [[Pig|porcine]] insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C-peptide of [[proinsulin]], however, differs much more among species; it is also a hormone, but a secondary one.<ref name=":1" />

Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is about 36000 Da in size. The six molecules are linked together as three dimeric units to form symmetrical molecule. An important feature is the presence of zinc atoms (Zn<sup>2+</sup>) on the axis of symmetry, which are surrounded by three water molecules and three histidine residues at position B10.<ref name=":0" /><ref name=":1" />

The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons; however, the monomer is a much faster-reacting drug because diffusion rate is inversely related to particle size. A fast-reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules.<ref name="pmid16158220">{{cite journal | vauthors = Dunn MF | title = Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review | journal = Biometals | volume = 18 | issue = 4 | pages = 295–303 | date = August 2005 | pmid = 16158220 | doi = 10.1007/s10534-005-3685-y | s2cid = 8857694 }}</ref> Insulin can aggregate and form [[fibrillar]] interdigitated [[beta-sheet]]s. This can cause injection [[amyloidosis]], and prevents the storage of insulin for long periods.<ref name="pmid19864624">{{cite journal | vauthors = Ivanova MI, Sievers SA, Sawaya MR, Wall JS, Eisenberg D | title = Molecular basis for insulin fibril assembly | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 45 | pages = 18990–5 | date = November 2009 | pmid = 19864624 | pmc = 2776439 | doi = 10.1073/pnas.0910080106 | bibcode = 2009PNAS..10618990I | doi-access = free }}</ref>