Editing Insulin (section)

=== Physiological effects ===
[[File:Insulin glucose metabolism ZP.svg|thumbnail|upright=1.8|'''Effect of insulin on glucose uptake and metabolism.''' Insulin binds to its receptor (1), which starts many protein activation cascades (2). These include translocation of Glut-4 transporter to the [[plasma membrane]] and influx of glucose (3), [[glycogen]] synthesis (4), [[glycolysis]] (5) and triglyceride synthesis (6).]]

[[File:Signal Transduction Diagram- Insulin.svg|thumb|upright=1.8|The insulin signal transduction pathway begins when insulin binds to the insulin receptor proteins. Once the transduction pathway is completed, the GLUT-4 storage vesicles becomes one with the cellular membrane. As a result, the GLUT-4 protein channels become embedded into the membrane, allowing glucose to be transported into the cell.]]

The actions of insulin on the global human metabolism level include:
* Increase of cellular intake of certain substances, most prominently glucose in muscle and [[adipose tissue]] (about two-thirds of body cells)<ref name="pmid21864752">{{cite journal | vauthors = Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis SA | title = Insulin effects in muscle and adipose tissue | journal = Diabetes Research and Clinical Practice | volume = 93 | issue = Suppl 1 | pages = S52–59 | date = August 2011 | pmid = 21864752 | doi = 10.1016/S0168-8227(11)70014-6 }}</ref>
* Increase of [[DNA replication]] and [[protein synthesis]] via control of amino acid uptake
* Modification of the activity of numerous [[enzymes]].

The actions of insulin (indirect and direct) on cells include:
* Stimulates the uptake of glucose –  Insulin decreases blood glucose concentration by inducing [[cellular glucose intake|intake of glucose]] by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell.<ref name="diabetesincontrol.com"/>
* Increased [[Fatty acid metabolism#Glycolytic endy products are used in the conversion of carbohydrates into fatty acids|fat synthesis]] – insulin forces fat cells to take in blood glucose, which is converted into [[triglyceride]]s; decrease of insulin causes the reverse.<ref name="pmid21864752" />
* Increased [[esterification]] of fatty acids – forces adipose tissue to make neutral fats (i.e., [[triglycerides]]) from fatty acids; decrease of insulin causes the reverse.<ref name="pmid21864752" />
* Decreased [[lipolysis]] in  – forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol; decrease of insulin causes the reverse.<ref name="pmid21864752" />
* Induced glycogen synthesis – When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that cannot exit the cell. At the same time, insulin inhibits the enzyme glucose-6-phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis.<ref>{{cite web|url=http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html|title=Physiologic Effects of Insulin|website=www.vivo.colostate.edu|language=en|access-date=1 June 2017|archive-date=7 May 2023|archive-url=https://web.archive.org/web/20230507054119/http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html|url-status=dead}}</ref>
* Decreased [[gluconeogenesis]] and [[glycogenolysis]] – decreases production of glucose from noncarbohydrate substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); decrease of insulin causes glucose production by the liver from assorted substrates.<ref name="pmid21864752" />
* Decreased [[proteolysis]] – decreasing the breakdown of protein<ref name="pmid21864752" />
* Decreased [[Autophagy (cellular)|autophagy]] – decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.<ref name="pmid17934054">{{cite journal | vauthors = Bergamini E, Cavallini G, Donati A, Gori Z | title = The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction | journal = Annals of the New York Academy of Sciences | volume = 1114 | issue =  1| pages = 69–78 | date = October 2007 | pmid = 17934054 | doi = 10.1196/annals.1396.020 | bibcode = 2007NYASA1114...69B | s2cid = 21011988 }}</ref>
* Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.<ref name="pmid21864752" />
* Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; decrease of insulin reduces flow by allowing these muscles to contract.<ref name="Zheng">{{cite journal | vauthors = Zheng C, Liu Z | title = Vascular function, insulin action, and exercise: an intricate interplay | journal = Trends in Endocrinology and Metabolism | volume = 26 | issue = 6 | pages = 297–304 | date = June 2015 | pmid = 25735473 | pmc = 4450131 | doi = 10.1016/j.tem.2015.02.002 }}</ref>
* Increase in the secretion of [[hydrochloric acid]] by parietal cells in the stomach.{{Citation needed|date=March 2017}}
* Increased potassium uptake – forces cells synthesizing [[glycogen]] (a very spongy, "wet" substance, that [[Glycogen#Structure|increases the content of intracellular water, and its accompanying K<sup>+</sup> ions]])<ref name="pmid1615908">{{cite journal | vauthors = Kreitzman SN, Coxon AY, Szaz KF |url= http://ajcn.nutrition.org/content/56/1/292S.full.pdf | title = Glycogen storage: illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition | journal = The American Journal of Clinical Nutrition | volume = 56 | issue = Suppl 1 | pages = 292S–93S | date = July 1992 | pmid = 1615908 | doi = 10.1093/ajcn/56.1.292S |archive-url= https://web.archive.org/web/20121018174037/http://ajcn.nutrition.org/content/56/1/292S.full.pdf |archive-date= 18 October 2012 }}</ref> to absorb potassium from the extracellular fluids; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood plasma.  This possibly occurs via insulin-induced translocation of the [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup>-ATPase]] to the surface of skeletal muscle cells.<ref>{{cite journal | vauthors = Benziane B, Chibalin AV | title = Frontiers: skeletal muscle sodium pump regulation: a translocation paradigm | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 295 | issue = 3 | pages = E553–58 | date = September 2008 | pmid = 18430962 | doi = 10.1152/ajpendo.90261.2008 | s2cid = 10153197 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Clausen T | title = Regulatory role of translocation of Na+-K+ pumps in skeletal muscle: hypothesis or reality? | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 295 | issue = 3 | pages = E727–28; author reply 729 | date = September 2008 | pmid = 18775888 | doi = 10.1152/ajpendo.90494.2008 | s2cid = 13410719 | doi-access =  }}</ref>
* Decreased renal sodium excretion.<ref>{{cite journal | vauthors = Gupta AK, Clark RV, Kirchner KA | title = Effects of insulin on renal sodium excretion | journal = Hypertension | volume = 19 | issue = Suppl 1 | pages = I78–82 | date = January 1992 | pmid = 1730458 | doi = 10.1161/01.HYP.19.1_Suppl.I78 }}</ref>
* In hepatocytes, insulin binding acutely leads to activation of protein phosphatase 2A (PP2A){{Citation needed|date=September 2023}}, which dephosphorylates the bifunctional enzyme [[Phosphofructokinase_2#PFKB1:_Liver,_muscle,_and_fetal | fructose bisphosphatase-2 (PFKB1)]],<ref name="Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG, Hue L_2004">{{cite journal | vauthors = Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG, Hue L | title = 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis | journal = Biochemical Journal | date = 1 August 2004 | volume = 381 | issue = 3 | pages = 561–579 | pmid = 15170386 | pmc = 1133864 | doi = 10.1042/BJ20040752}}</ref> activating the phosphofructokinase-2 (PFK-2) active site. PFK-2 increases production of fructose 2,6-bisphosphate. [[Fructose 2,6-bisphosphate]] allosterically activates [[PFK-1]], which favors glycolysis over gluconeogenesis. Increased glycolysis increases the formation of [[malonyl-CoA]], a molecule that can be shunted into lipogenesis and that allosterically inhibits of [[Carnitine palmitoyltransferase I | carnitine palmitoyltransferase I (CPT1)]], a mitochondrial enzyme necessary for the translocation of fatty acids into the intermembrane space of the mitochondria for fatty acid metabolism.<ref name="Wang Y, Yu W, Li S, Guo D, He J, Wang Y_2022">{{cite journal | vauthors = Wang Y, Yu W, Li S, Guo D, He J, Wang Y | title = Acetyl-CoA Carboxylases and Diseases | journal = Frontiers in Oncology | date = 11 March 2022 | volume = 12 | pmid = 35359351 | pmc = 8963101 | doi = 10.3389/fonc.2022.836058 | doi-access = free }}</ref>

Insulin also influences other body functions, such as [[Capacitance of blood vessels|vascular compliance]] and [[cognition]]. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular.<ref name="pmid15288712">{{cite journal |vauthors=Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W |url=https://www.gwern.net/docs/nootropics/2004-benedict.pdf |title=Intranasal insulin improves memory in humans |journal=Psychoneuroendocrinology |volume=29 |issue=10 |pages=1326–1334 |date=November 2004 |pmid=15288712 |doi=10.1016/j.psyneuen.2004.04.003 |s2cid=20321892}}</ref> Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of [[Homeostasis|homeostatic or regulatory processes]] in the human body.<ref name="pmid20876713">{{cite journal |vauthors=Benedict C, Brede S, Schiöth HB, Lehnert H, Schultes B, Born J, Hallschmid M |title=Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men |journal=Diabetes |volume=60 |issue=1 |pages=114–118 |date=January 2011 |pmid=20876713 |pmc=3012162 |doi=10.2337/db10-0329}}</ref> Insulin also has stimulatory effects on [[gonadotropin-releasing hormone]] from the [[hypothalamus]], thus favoring [[fertility]].<ref name="pmid24173881">{{cite journal |vauthors=Comninos AN, Jayasena CN, Dhillo WS | title = The relationship between gut and adipose hormones, and reproduction |journal=Human Reproduction Update |volume=20 |issue=2 |pages=153–174 |year=2014 |pmid=24173881 |doi=10.1093/humupd/dmt033 |s2cid=18645125 |doi-access=free}}</ref>