Editing Pancreas (section)

== Function ==

The pancreas is involved in [[blood sugar control]] and [[metabolism]] within the body, and also in the secretion of substances (collectively [[pancreatic juice]]) that help [[digestion]]. These functions are divided into an [[endocrine gland|endocrine]] role, relating to the secretion of [[insulin]] and other [[hormone]]s within pancreatic islets that help control blood sugar levels and metabolism, and an [[Exocrine gland|exocrine]] role, relating to the secretion of [[Pancreatic enzymes|pancreatic digestive enzymes]].{{sfn|Wheater's Histology|2013|pp=287-291}}

===Blood glucose regulation===
{{See also|Pancreatic islets}}
[[File:Negative Feedback Gif.gif|thumb|The pancreas maintains constant blood glucose levels (shown as the waving line). When the blood glucose level is too high, the pancreas secretes insulin and when the level is too low, the pancreas secretes glucagon.]]
Cells within the pancreas help to maintain blood glucose levels ([[homeostasis]]). The cells that do this are located within the pancreatic islets that are present throughout the pancreas. When blood glucose levels are low, [[alpha cell]]s secrete [[glucagon]], which increases blood glucose levels. When blood glucose levels are high [[beta cell]]s secrete [[insulin]] to decrease glucose in blood. [[Delta cell]]s in the islet also secrete [[somatostatin]] which decreases the release of insulin and glucagon.{{sfn|Wheater's Histology|2013|pp=332-333}}

Glucagon acts to increase glucose levels by promoting the [[gluconeogenesis|creation of glucose]] and the [[glycogenolysis|breakdown of glycogen]] to glucose in the liver. It also decreases the uptake of glucose in fat and muscle. Glucagon release is stimulated by low blood glucose or insulin levels, and during exercise.{{sfn|Harrison's|2015|pp=2853-4}} Insulin acts to decrease blood glucose levels by facilitating uptake by cells (particularly [[skeletal muscle]]), and promoting its use in the creation of proteins, fats and carbohydrates. Insulin is initially created as a precursor form called [[preproinsulin]]. This is converted to [[proinsulin]] and cleaved by [[C-peptide]] to [[insulin]] which is then stored in granules in beta cells. Glucose is taken into the beta cells and degraded. The end effect of this is to cause [[depolarisation]] of the cell membrane which stimulates the release of the insulin.{{sfn|Harrison's|2015|pp=2853-4}}

<!--Influences-->The main factor influencing the secretion of insulin and glucagon are the levels of glucose in blood plasma.<ref name=Ganongs2019Islets>{{Cite book|title=Ganong's review of medical physiology|author1=Barrett, Kim E.|others=Barman, Susan M.,, Brooks, Heddwen L., Yuan, Jason X.-J.|isbn=978-1-260-12240-4|edition=26th|location=New York|oclc=1076268769|year=2019|pages=433–437|section=Regulation of Insulin Secretion; Glucagon}}</ref> Low blood sugar stimulates glucagon release, and high blood sugar stimulates insulin release. Other factors also influence the secretion of these hormones. Some [[amino acid]]s, that are byproducts of the digestion of [[protein]], stimulate insulin and glucagon release. Somatostatin acts as an inhibitor of both insulin and glucagon. The [[autonomic nervous system]] also plays a role. Activation of [[Beta-2 adrenergic receptor|Beta-2 receptors]] of the [[sympathetic nervous system]] by [[catecholamine]]s secreted from sympathetic nerves stimulates secretion of insulin and glucagon,<ref name=Ganongs2019Islets /><ref name=GuytonHall2016>{{cite book |last1=Hall |first1=John E |title=Guyton and Hall textbook of medical physiology |date=2016 |publisher=Elsevier |location=Philadelphia |isbn=978-1-4557-7016-8 |edition=13th|pages=990–994}}</ref> whereas activation of [[Alpha-1 adrenergic receptors|Alpha-1 receptors]] inhibits secretion.<ref name=Ganongs2019Islets /> [[Muscarinic acetylcholine receptor M3|M3 receptors]] of the [[parasympathetic nervous system]] act when stimulated by the right [[vagus nerve]] to stimulate release of insulin from beta cells.<ref name=Ganongs2019Islets />

===Digestion===
[[File:1820 The Pancreas.jpg|thumb|The pancreas has a role in digestion, highlighted here. Ducts in the pancreas (green) conduct digestive enzymes into the duodenum. This image also shows a [[pancreatic islet]], part of the endocrine pancreas, which contains cells responsible for secretion of [[insulin]] and [[glucagon]].]]
The pancreas plays a vital role in the [[digestive system]]. It does this by secreting [[pancreatic juice]], a fluid that contains digestive enzymes, into the [[duodenum]], the first part of the [[small intestine]] that receives food from the [[stomach]]. These enzymes help to break down carbohydrates, proteins and lipids (fats). This is the [[exocrine]] role of the pancreas. The cells responsible for this are [[centroacinar cell]]s arranged in clusters called [[acini]]. Secretions into the middle of the acinus accumulate in [[intralobular ducts]], which drain to the main [[pancreatic duct]], which drains directly into the [[duodenum]]. About 1.5–3 liters of fluid are secreted in this manner every day.{{sfn|Gray's|2008|pp=1183-1190}}{{sfn|Harrison's|2015|pp=2086-2102}}

The cells in each acinus are filled with granules containing the digestive enzymes. These are secreted in an inactive form termed [[zymogen]]s or proenzymes. When released into the duodenum, they are activated by the enzyme [[enterokinase]] present in the lining of the duodenum. The proenzymes are cleaved, creating a cascade of activating enzymes.{{sfn|Harrison's|2015|pp=2086-2102}}
* [[Protease|Enzymes that break down proteins]] begin with activation of [[trypsinogen]] to [[trypsin]]. The free trypsin then cleaves the rest of the trypsinogen, as well as [[chymotrypsinogen]] to its active form [[chymotrypsin]].{{sfn|Harrison's|2015|pp=2086-2102}}
* Enzymes secreted involved in the digestion of fats include [[pancreatic lipase|lipase]], [[phospholipase A2]], [[lysophospholipase]], and [[Sterol esterase|cholesterol esterase]].{{sfn|Harrison's|2015|pp=2086-2102}}
* Enzymes that break down starch and other carbohydrates include [[amylase]].{{sfn|Harrison's|2015|pp=2086-2102}}

These enzymes are secreted in a fluid rich in [[bicarbonate]]. Bicarbonate helps maintain an [[alkaline]] pH for the fluid, a pH in which most of the enzymes act most efficiently, and also helps to neutralise the stomach acids that enter the duodenum.{{sfn|Harrison's|2015|pp=2086-2102}} Secretion is influenced by hormones including [[secretin]], [[cholecystokinin]], and [[vasoactive intestinal peptide|VIP]], as well as [[acetylcholine]] stimulation from the [[vagus nerve]]. Secretin is released from the [[S cell]]s which form part of the lining of the duodenum in response to stimulation by gastric acid. Along with VIP, it increases the secretion of enzymes and bicarbonate. Cholecystokinin is released from [[Ito cell]]s of the lining of the duodenum and jejunum mostly in response to long chain fatty acids, and increases the effects of secretin.{{sfn|Harrison's|2015|pp=2086-2102}} At a cellular level, bicarbonate is secreted from centroacinar and ductal cells through a sodium and bicarbonate [[cotransporter]] that acts because of membrane depolarisation caused by the [[cystic fibrosis transmembrane conductance regulator]]. Secretin and VIP act to increase the opening of the cystic fibrosis transmembrane conductance regulator, which leads to more membrane depolarisation and more secretion of bicarbonate.{{sfn|Harrison's|2015|pp=2090}}{{sfn|Beger's|2018|pp=16,57}}<ref name="Pandol2014">{{cite journal |last1=Pandol |first1=Stephen J |title=The Exocrine Pancreas |journal=Colloquium Series on Integrated Systems Physiology: From Molecule to Function |volume=3 |issue=2 |date=2011 |pages=1–64 |id={{NCBIBook|NBK54128}} |pmid=21634067 |doi=10.4199/C00026ED1V01Y201102ISP014 |doi-access=free }}</ref>

A variety of mechanisms act to ensure that the digestive action of the pancreas does not act to digest pancreatic tissue itself. These include the secretion of inactive enzymes (zymogens), the secretion of the protective enzyme [[trypsin inhibitor]], which inactivates trypsin, the changes in pH that occur with bicarbonate secretion that stimulate digestion only when the pancreas is stimulated, and the fact that the low calcium within cells causes inactivation of trypsin.{{sfn|Harrison's|2015|pp=2086-2102}}

===Additional functions===
The pancreas also secretes [[vasoactive intestinal peptide]] and [[pancreatic polypeptide]]. [[Enterochromaffin cell]]s of the pancreas secrete the hormones [[motilin]], [[serotonin]], and [[substance P]].{{sfn|Wheater's Histology|2013|pp=332-333}} It has been demonstrated that pancreatic tissue is a strong accumulator and secretor in the intestine of radioactive cesium ([[Cs-137]]).<ref>{{Cite journal |last=Bandazhevsky Y.I. |year=2003 |title=Chronic Cs-137 incorporation in children's organs. |journal=Swiss Med. Wkly. |volume=133 |issue=35–36 |pages=488–90 |doi=10.4414/smw.2003.10226 |pmid=14652805 |s2cid=28184979 |doi-access=free}}</ref><ref>{{cite journal |last1=Venturi |first1=Sebastiano |title=Cesium in Biology, Pancreatic Cancer, and Controversy in High and Low Radiation Exposure Damage—Scientific, Environmental, Geopolitical, and Economic Aspects |journal=International Journal of Environmental Research and Public Health |date=January 2021 |volume=18 |issue=17 |page=8934 |doi=10.3390/ijerph18178934 |pmid=34501532 |language=en|pmc=8431133 |doi-access=free }}</ref>