Editing Insulin (section)

=== Synthesis ===
[[File:Insulin path.svg|thumb|upright=1.8|Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Both C-peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale.]]

Insulin is synthesized as an inactive [[Protein precursor|precursor]] molecule, a 110 amino acid-long protein called preproinsulin.<!-- Cite. Merged AA length from [[Preproinsulin]] --> Preproinsulin is [[translation (biology)|translated]] directly into the rough [[endoplasmic reticulum]] (RER), where its [[signal peptide]] is removed by [[signal peptidase]] to form [[proinsulin]].<ref name=Tokarz2018/> As the proinsulin [[protein folding|folds]], opposite ends of the protein, called the "A-chain" and the "B-chain", are fused together with three [[disulfide bond]]s.<ref name=Tokarz2018/> Folded proinsulin then transits through the [[Golgi apparatus]] and is packaged into specialized [[Vesicle (biology and chemistry)#Secretory vesicles|secretory vesicle]]s.<ref name=Tokarz2018/> In the granule, proinsulin is cleaved by [[Proprotein convertase 1|proprotein convertase 1/3]] and [[proprotein convertase 2]], removing the middle part of the protein, called the "[[C-peptide]]".<ref name=Tokarz2018/> Finally, [[carboxypeptidase E]] removes two pairs of amino acids from the protein's ends, resulting in active insulin – the insulin A- and B- chains, now connected with two disulfide bonds.<ref name=Tokarz2018/><!-- the figure in this shows the two bonds but the text doesn't explicitly say it. Probably best to find a better source -->

The resulting mature insulin is packaged inside mature granules waiting for metabolic signals (such as leucine, arginine, glucose and mannose) and [[Vagus nerve stimulation|vagal nerve stimulation]] to be exocytosed from the cell into the circulation.<ref name = "Najjar_2001">{{cite book | vauthors = Najjar S | chapter = Insulin Action: Molecular Basis of Diabetes | date = 2003 | title = Encyclopedia of Life Sciences | publisher = John Wiley & Sons | doi = 10.1038/npg.els.0001402 | isbn = 978-0-470-01617-6 }}</ref>

Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to [[Alzheimer's disease]].<ref name="urlResearchers discover link between insulin and Alzheimers">{{cite web | url = http://www.eurekalert.org/pub_releases/2005-03/l-rdl030205.php | title = Researchers discover link between insulin and Alzheimer's | vauthors = Gustin N | date = 7 March 2005 | work = EurekAlert! | publisher = American Association for the Advancement of Science | access-date = 1 January 2009}}</ref><ref name="pmid15750214">{{cite journal | vauthors = de la Monte SM, Wands JR |url= https://www.alzforum.org/sites/default/files/legacy/res/for/journal/delamonte/jad00401.pdf | title = Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease | journal = Journal of Alzheimer's Disease | volume = 7 | issue = 1 | pages = 45–61 | date = February 2005 | pmid = 15750214 | doi = 10.3233/JAD-2005-7106 }}</ref><ref name="pmid15750215">{{cite journal | vauthors = Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM | title = Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease—is this type 3 diabetes? | journal = Journal of Alzheimer's Disease | volume = 7 | issue = 1 | pages = 63–80 | date = February 2005 | pmid = 15750215 | doi = 10.3233/jad-2005-7107| s2cid = 28173722 | url = https://www.alzforum.org/sites/default/files/legacy/res/for/journal/delamonte/jad00400.pdf }}</ref>

Insulin release is stimulated also by beta-2 receptor stimulation and inhibited by alpha-1 receptor stimulation. In addition, cortisol, glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by [[hormone-sensitive lipase]] in adipose tissue.<ref name="stryer" />