The Pancreas
Written by Iris Levink
Major Discoveries in Pancreatic Physiology1
Anatomy of the Pancreas
The General Shape
The pancreas is a retroperitoneal gland, measuring approximately 12-15 cm in length and 2.5 cm in thickness. Based on its embryonic development it is divided into the uncinate process, head, body and tail. The uncinate process and head are near the duodenum, whilst the body and tail extend tapered towards the spleen. This glandular organ is connected to the duodenum through two main ducts, supporting its digestive and hormonal functions.2
1. Acini
The pancreas consists of glandular epithelial cells arranged in small clusters known as acini, forming the exocrine portion that accounts for 99% of the organ’s tissue. These acinar cells are responsible for producing pancreatic juice, a blend of digestive enzymes and fluids.2
2. Pancreatic Islet Cells
The remaining 1% of the organ’s structure comprises the pancreatic islets, or islets of Langerhans, making up the endocrine component. These cells secrete hormones such as glucagon, insulin, somatostatin and pancreatic polypeptide, which are essential for the body’s metabolic regulation1-3. This has been summarised in Table 1.
Table 1 – Pancreatic cells and their function1
3. Pancreatic ducts
Pancreatic juice, important for digestion, is produced by the exocrine cells of the pancreas.1,2 In response to hormones secreted by the duodenum, the pancreatic juice is first released into small ducts which meet in one main pancreatic duct. An accessory duct divaricates near the duodenum, creating two orifices through which pancreatic juice is released into the duodenum. The pancreatic duct joins the common bile duct from the liver and gallbladder, and enters the duodenum as one dilated common duct called the ampulla of Vater.2
4. Ampulla of Vater
The ampulla of Vater introduces pancreatic and bile secretions into the duodenum via relaxation of the sphincter of Oddi, which is located roughly 10 cm below the pyloric sphincter of the stomach and pathway for pancreatic juices entering the duodenum about 2.5 cm above the ampulla of Vater.1,2
Physiology of the Pancreas
The pancreas plays a dual role in human physiology by regulating both digestion (exocrine function) and glucose metabolism (endocrine function).2
Exocrine Function
Pancreatic Secretions
The pancreas adapts its secretory output based on dietary intake, producing approximately two litres of enzyme- and electrolyte-rich secretion (‘pancreatic juice’) daily in adults. After stimulation, the secretion rate increases from 0.2-0.3 ml/min to over ten times the resting rate. This output varies during digestion, influenced by peptide hormones like cholecystokinin (CCK) and signals from the vagus nerve, which increase enzyme production from acinar cells. Secretin predominantly drives bicarbonate release from duct cells to facilitate digestion.1,3
Inorganic Components
The main inorganic components of pancreatic juice are water, sodium, potassium, chloride and bicarbonate. The bicarbonate ensures the secretion maintains an alkaline pH of approximately 8, which neutralises the acid chyme from the stomach to optimise the pH of the intestinal lumen for enzyme activity.1,3
Pancreatic Enzymes
Digestive enzymes account for about 90% of the proteins in pancreatic secretions, with trypsin being the most important enzyme. Acinar cells produce all proteolytic enzymes as inactive precursors, or zymogens, which become active in the duodenum. The enzyme enteropeptidase (enterokinase) localised in the intestinal brush border membrane, breaks down trypsinogen into active trypsin. Trypsin can then convert trypsinogen and all other proenzymes into their active form. Premature activation within the pancreas can cause autodigestion and lead to acute pancreatitis.1
Regulation of Pancreatic Secretions
The regulation of pancreatic exocrine secretion involves a complex interplay of nervous and hormonal signals. Secretion stimulated by food intake is divided into cephalic, gastric and intestinal phases (Table 2)1:
Cephalic Phase: Initiated by efferent fibres of the vagus nerve, this phase involves the parasympathetic release of acetylcholine, which stimulates enzyme secretion from acinar cells. Vasoactive intestinal polypeptide (VIP) and Gastrin-releasing peptide (GRP) also contribute, enhancing enzyme and bicarbonate secretion.1
Gastric Phase: Triggered by stomach distension, this phase prompts an enzyme-rich secretion through a vagovagal reflex.1
Intestinal Phase: This phase is initiated with chyme entry into the duodenum. Secretin is released in response to acidification and in turn stimulates bicarbonate secretion. Cholecystokinin (CCK), the primary humoral mediator for digestive enzyme secretion, is released in response to fats and proteins in the chyme.1 CCK also increases the effect of secretin.1
This regulatory framework ensures pancreatic secretions are adjusted to the body’s digestive needs, highlighting the organ’s vital role in nutrient absorption and gastrointestinal health.1
Table 2: Gastrointestinal peptides and their influence on the endocrine and exocrine pancreas1
Endocrine Function
The pancreas serves as a pivotal endocrine organ through the hormone-producing cells of the pancreatic islets (islets of Langerhans).1 Alpha cells produce glucagon, β cells produce insulin, delta cells produce somatostatin and F cells produce pancreatic polypeptides (Table 1).1 The main functions of these hormones are to regulate blood glucose levels and growth by storing ingested nutrients, such as glycogen and lipids in case of excess in response to insulin, and release these energy reserves during periods of hunger in response to glucagon.1
Insulin
Produced by beta cells, which constitute 50-80% of the cells in the islet system, insulin is the primary glucose-lowering hormone in the body.1 Insulin is first produced as an inactive proenzyme and later converted into its biologically active form within the Golgi apparatus and the beta-cell granules via cleavage of the C-peptide by insulin convertase.1 Its secretion is triggered by an increase in extracellular glucose levels.1 It is further regulated by enterohormones, such as glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1), which stimulate its secretion, whilst somatostatin, ghrelin, leptin and catecholamines inhibit it.1 The main effect of insulin is to facilitate glucose uptake into muscle and adipose tissue, thereby lowering blood glucose levels.1 By activating glycogen synthase and phosphodiesterase, insulin increases glycogen synthesis, reduces glycogenolysis in liver and muscle cells, and inhibits hepatic gluconeogenesis.1 Additionally, insulin inhibits lipolysis and promotes triglyceride synthesis in adipose tissue.1
Glucagon
Glucagon, originating from alpha cells as preproglucagon, plays a crucial role in glucose regulation, acting inversely to insulin.1 Glucagon is formed from a precursor molecule, preproglucagon, and converted by pancreatic prohormone convertases into the biologically active glucagon.1 Besides the glucagon sequence, preproglucagon also contains the amino acid sequences for two other peptide hormones known as GLP1 and GLP2 (GLP: glucagon-like peptide).1 In addition to alpha cells, the central nervous system and intestinal mucosa produce preproglucagon (enteroglucagon).1 This mechanism (the incretin effect) explains why oral glucose leads to higher blood insulin levels than parenteral glucose.1
Like insulin, glucagon secretion depends on blood glucose levels.2 However, unlike insulin, a decrease in glucose concentration stimulates glucagon secretion, whereas an increase in glucose concentration inhibits glucagon release.1 Glucagon acts as an insulin antagonist by increasing glycogenolysis and inhibiting gluconeogenesis.1 Glucagon also promotes the uptake of amino acids into the liver cell.1
Somatostatin
Somatostatin broadly inhibits both endocrine and exocrine functions.1 It suppresses the release of pituitary growth hormone (somatotropin) and inhibits the secretion of both insulin and glucagon.1 Somatostatin also inhibits gastric acid secretion and the release of both enzymes and bicarbonate from the pancreas, playing an important role in digestive regulation.1
Pancreatic Polypeptide
Synthesised primarily by F cells in the islets of Langerhans within the pancreas head.1 It has an inhibitory effect on the secretion of bicarbonate and digestive enzymes from the pancreas and gallbladder contraction.1 Furthermore, it is involved in the regulation of appetite through its action on central nervous system receptors.1
References
- Rodeck B. Pädiatrische Gastroenterologie, Hepatologie und Ernährung. 2nd ed. Springer; 2012.
- Bardeesy N, DePinho RA. Nat Rev Cancer. 2002;2(12):897-909.
- Tyler Stevens, Darwin L Conwell. November 8th, 2023. Accessed March 2024.
https://www.uptodate.com/contents/exocrine-pancreatic-insufficiency#H2482574495
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