Editing Insulin-like growth factor 1 (section)

== Mechanism of action ==
{{See also|Hypothalamic–pituitary–somatic axis}}

IGF-1 is a primary [[Mediator (coactivator)|mediator]] of the effects of [[growth hormone]] (GH). Growth hormone is made in the [[anterior pituitary]] gland, released into the [[bloodstream]], and then stimulates the [[liver]] to produce IGF-1. IGF-1 then stimulates systemic [[body growth]], and has [[Cell growth|growth]]-promoting effects on almost every [[cell (biology)|cell]] in the body, especially skeletal [[muscle]], [[cartilage]], [[bone]], [[liver]], [[kidney]], [[nerve]], [[skin]], [[hematopoietic]], and [[lung]] cells. In addition to its [[insulin]]-like effects (insulin being the main [[Anabolism|anabolic]] [[hormone]] in the body),<ref name="Biochemistry">{{cite book | vauthors = Voet D, Voet JG | title = Biochemistry | date = 2011 | publisher = Wiley | location = New York | edition = 4th }}</ref> IGF-1 can also regulate cellular [[DNA synthesis]].<ref>{{cite journal | vauthors = Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D | title = Circulating levels of IGF-1 directly regulate bone growth and density | journal = The Journal of Clinical Investigation | volume = 110 | issue = 6 | pages = 771–781 | date = September 2002 | pmid = 12235108 | pmc = 151128 | doi = 10.1172/JCI15463 }}</ref>

IGF-1 [[Receptor (biochemistry)#Binding and activation|binds]] to at least two [[cell surface]] [[receptor tyrosine kinase]]s: the [[IGF-1 receptor]] (IGF1R), and the [[insulin receptor]]. Its primary action is mediated by binding to its specific receptor, IGF1R, which is present on the surface of several cell types in a multitude of tissues. Binding to the IGF1R initiates [[intracellular signaling]]. IGF-1 is one of the most potent natural [[Activator (genetics)|activators]] of the [[Akt]] [[Signal transduction|signaling pathway]], a stimulator of cell growth and [[Cell proliferation|proliferation]], and a potent [[Inhibitor protein|inhibitor]] of [[Apoptosis|programmed cell death]].<ref>{{cite journal | vauthors = Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G, Calabretta B, Baserga R | title = Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 7203–7215 | date = October 1999 | pmid = 10490655 | pmc = 84713 | doi = 10.1128/mcb.19.10.7203 }}</ref><ref>{{cite journal | vauthors = Juin P, Hueber AO, Littlewood T, Evan G | title = c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release | journal = Genes & Development | volume = 13 | issue = 11 | pages = 1367–1381 | date = June 1999 | pmid = 10364155 | pmc = 316765 | doi = 10.1101/gad.13.11.1367 }}</ref> The IGF-1 receptor and insulin receptor are two closely related members of a [[Transmembrane protein|transmembrane]] [[Tetrameric protein|tetrameric]] tyrosine kinase receptor family. They control vital [[brain functions]], such as [[survival]], growth, [[energy metabolism]], [[longevity]], [[neuroprotection]] and [[neuroregeneration]].<ref>{{cite journal | vauthors = Moloney AM, Griffin RJ, Timmons S, O'Connor R, Ravid R, O'Neill C | title = Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling | journal = Neurobiology of Aging | volume = 31 | issue = 2 | pages = 224–243 | date = February 2010 | pmid = 18479783 | doi = 10.1016/j.neurobiolaging.2008.04.002 | s2cid = 14265087 }}</ref>
=== Metabolic effects ===

As a major [[growth factor]], IGF-1 is responsible for stimulating growth of all cell types, and causing significant [[Metabolism|metabolic effects]].<ref name="pmid22682639">{{cite journal | vauthors = Clemmons DR | title = Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes | journal = Endocrinology and Metabolism Clinics of North America | volume = 41 | issue = 2 | pages = 425–43, vii-viii | date = June 2012 | pmid = 22682639 | pmc = 3374394 | doi = 10.1016/j.ecl.2012.04.017 }}</ref> One important metabolic effect of IGF-1 is signaling cells that sufficient [[Nutrient|nutrients]] are available for them to undergo [[hypertrophy]] and [[cell division]].<ref name="pmid4600536">{{cite journal | vauthors = Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER | title = Role of IGF-I signaling in muscle bone interactions | journal = Bone | volume = 80 | pages = 79–88 | date = November 2015 | pmid = 26453498 | pmc = 4600536 | doi = 10.1016/j.bone.2015.04.036 }}</ref> Its effects also include [[Enzyme inhibitor|inhibiting]] [[cell apoptosis]] and increasing the production of [[Cellular protein|cellular proteins]].<ref name="pmid4600536"/> IGF-1 receptors are ubiquitous, which allows for metabolic changes caused by IGF-1 to occur in all cell types.<ref name="pmid22682639"/> IGF-1's metabolic effects are far-reaching and can coordinate [[Protein metabolism|protein]], [[Carbohydrate metabolism|carbohydrate]], and [[fat metabolism]] in a variety of different cell types.<ref name="pmid22682639"/> The regulation of IGF-1's metabolic effects on target tissues is also coordinated with other hormones such as growth hormone and insulin.<ref>{{cite journal | vauthors = Clemmons DR | title = The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity | journal = The Journal of Clinical Investigation | volume = 113 | issue = 1 | pages = 25–27 | date = January 2004 | pmid = 14702105 | pmc = 300772 | doi = 10.1172/JCI200420660 }}</ref>

=== The IGF system ===

IGF-1 is part of the insulin-like growth factor (IGF) system.<ref name="García-Mato_2021" /> This system consists of three [[Ligand (biochemistry)|ligands]] ([[insulin]], IGF-1 and [[Insulin-like growth factor 2|IGF-2]]), two [[tyrosine kinase receptors]] ([[insulin receptor]] and [[IGF-1R]] receptor) and six ligand binding proteins ([[Insulin-like growth factor-binding protein|IGFBP]] 1–6).<ref name="García-Mato_2021">{{cite journal | vauthors = García-Mato Á, Cervantes B, Murillo-Cuesta S, Rodríguez-de la Rosa L, Varela-Nieto I | title = Insulin-like Growth Factor 1 Signaling in Mammalian Hearing | journal = Genes | volume = 12 | issue = 10 | pages = 1553 | date = September 2021 | pmid = 34680948 | pmc = 8535591 | doi = 10.3390/genes12101553 | doi-access = free }}</ref> Together they play an essential role in [[Cell proliferation|proliferation]], [[Cell survival|survival]], regulation of [[cell growth]] and affect almost every [[organ system]] in the body.<ref>{{cite journal | vauthors = Annunziata M, Granata R, Ghigo E | title = The IGF system | journal = Acta Diabetologica | volume = 48 | issue = 1 | pages = 1–9 | date = March 2011 | pmid = 21042815 | doi = 10.1007/s00592-010-0227-z | s2cid = 24843614 }}</ref>

Similarly to IGF-1, [[IGF-2]] is mainly produced in the [[liver]] and after it is released into [[Blood circulation|circulation]], it stimulates growth and cell proliferation. IGF-2 is thought to be a [[Fetus|fetal]] growth factor, as it is essential for a normal [[Human embryonic development|embryonic development]] and is highly [[Gene expression|expressed]] in embryonic and [[Infant|neonatal]] [[Tissue (biology)|tissues]].<ref>{{cite book | vauthors = Winston BW, Ni A, Aurora RC | chapter = Insulin-like Growth Factors | veditors = Laurent GJ, Shapiro SD | title = Encyclopedia of Respiratory Medicine |date=2006 |pages=339–346 |doi=10.1016/B0-12-370879-6/00453-1 | isbn = 978-0-12-370879-3 | quote = GF-II appears to be essential for normal embryonic development and, as such, IGF-II is thought to be a fetal growth factor. IGF-II is highly expressed in embryonic and neonatal tissues and promotes proliferation of many cell types primarily of fetal origin.  }}</ref>

=== Variants ===
A [[splice variant]] of IGF-1 sharing an identical mature region, but with a different E domain is known as ''mechano-growth factor'' (MGF).<ref name="pmid17581790">{{cite journal | vauthors = Carpenter V, Matthews K, Devlin G, Stuart S, Jensen J, Conaglen J, Jeanplong F, Goldspink P, Yang SY, Goldspink G, Bass J, McMahon C | title = Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction | journal = Heart, Lung & Circulation | volume = 17 | issue = 1 | pages = 33–39 | date = February 2008 | pmid = 17581790 | doi = 10.1016/j.hlc.2007.04.013 }}</ref>