28: Gastrointestinal Hormones Flashcards
What are the 3 stimulators of motilin secretion?
- Duodenal acid
- Food
- Vagus input
[Wikipedia: Control of motilin secretion is largely unknown, although some studies suggest that an alkaline pH in the duodenum stimulates its release. It is interesting to note, however, that at low pH it inhibits gastric motor activity, whereas at high pH it has a stimulatory effect. Some studies in dogs have shown that motilin is released during fasting or interdigestive period, and intake of food during this period can prevent the secretion of motilin. Intravenous injection of glucose, which increases the release of insulin, is also found to inhibit cyclic elevation of plasma motilin. Other studies on dogs have also suggested that motilin acted as endogenous ligand in positive feedback mechanism to stimulate the release of more motilin.]
Where is glucagon produced?
Pancreas
What are the body’s 3 responses to gastrin secretion?
- Increased secretion of HCl
- Increased secretion of intrinsic factor
- Increased secretion of pepsinogen
[UpToDate: Gastrin is a primary physiologic mediator of gastric acid secretion. The human stomach secretes approximately 2 to 3 liters of acid-rich fluid per day. The regulation of acid secretion is influenced by the central, peripheral, and enteric nervous systems and multiple chemical messengers including gastrin, histamine, somatostatin, and acetylcholine.
The major cellular determinants of acid secretion involve the antral gastrin-secreting G cell, the enterochromaffin-like (ECL) cell of the stomach that secretes histamine, and the somatostatin-secreting D cell. The acid-secreting parietal cell possesses receptors for acetylcholine, histamine, and gastrin. Although activation of all three of these receptors can stimulate acid secretion, the most important mechanism of acid release occurs via stimulation of the ECL cell to secrete histamine, which in turn stimulates the parietal cell. The ECL cell receives stimulatory signals from gastrin and inhibitory signals from somatostatin. Somatostatin also provides inhibitory signals to antral G cells.
The CCK2 receptor can be found on pancreatic islet cells, and hypergastrinemia has been associated with islet cell hyperplasia and enhanced insulin secretion. In animals, coadministration of gastrin and glucagon-like peptide-1 can restore normoglycemia in diabetic mice, suggesting that gastrin may have incretin-like effects.]
Which cells produce glucagon?
Alpha cells
What stimulates Vasoactive intestinal peptide (VIP) secretion?
- Fat
- Acetylcholine
Which cells produce secretin?
S cells of the duodenum
[UpToDate: Similar to other gastrointestinal peptides, secretin is amidated at the C-terminus. It is the founding member of the secretin/glucagon/vasoactive intestinal polypeptide family of gastrointestinal hormones. The gene structure of preprosecretin contains an N-terminal signal peptide, a short peptide sequence, secretin, and a C-terminal extension peptide. The gene encoding secretin is selectively expressed in specialized enteroendocrine cells of the small intestine, called S cells. The details of secretin gene transcriptional control have been studied in secretin-producing islet cells.
Immunocytochemistry has demonstrated that secretin-producing cells are found along the small intestine. Other sites shown to produce secretin mRNA include the hypothalamus, cortex, cerebellum, and brainstem.]
What are the body’s 7 responses to glucagon secretion?
- Glycogenolysis
- Gluconeogenesis
- Lipolysis
- Ketogenesis
- Decrease in gastric acid secretion
- Decrease in gastrointestinal motility
- Relaxes sphincter of Oddi
What is the body’s response to insulin secretion?
- Cellular glucose uptake
- Promotes protein synthesis
[UpToDate: Insulin has a number of effects on glucose metabolism, including inhibition of glycogenolysis and gluconeogenesis, increased glucose transport into fat and muscle, increased glycolysis in fat and muscle, and stimulation of glycogen synthesis.
Insulin serves to coordinate the use of alternative fuels (glucose and free fatty acids) to meet the energy demands of the organism during cycles of feeding and fasting, and in response to exercise. In addition, insulin facilitates transport of amino acids into hepatocytes, skeletal muscle, and fibroblasts, which results in an increase in protein synthesis.
Insulin has actions beyond the realm of energy metabolism, including actions on steroidogenesis, vascular function, fibrinolysis, and growth.]
What is the name of the somatostatin analogue that can be used to decrease pancreatic fistula output?
Octreotide
[UpToDate: The clinical utility of somatostatin is hampered by its short half-life in the circulation (less than three minutes). As a result, octreotide acetate, a synthetic peptide that maintained the biological activity of somatostatin yet remained active for over 90 minutes was produced. Octreotide is much more stable in the circulation and is more potent in many of the inhibitory actions than native somatostatin. The clinical use of octreotide has been established for a number of indications.
Somatostatin analogues, somatostatin LAR (Sandostatin LAR) and lanreotide-PR (Somatuline PR), have also simplified treatment with somatostatin analogues. These agents are slow-release formulations that require only monthly injection and supply high-dose, stable serum levels of octreotide. These agents provide for improved patient compliance since they are administered on a weekly to monthly schedule depending upon the indication.
Somatostatin inhibits pancreatic exocrine and endocrine secretion. A possible role in preventing post-ERCP pancreatitis has also been suggested. Somatostatin receptor agonists have been investigated in a number of disorders of the pancreas, including acute pancreatitis and pancreatic fistulae. However, the results of many studies of acute pancreatitis indicate no clear benefit on the clinical utility of either somatostatin or octreotide in improving pancreatic fistulae drainage, or enterocutaneous fistulae. A meta-analysis suggested that somatostatin analogues may reduce complications following pancreatic surgery but did not reduce overall mortality.]
What is the body’s response to pancreatic polypeptide secretion?
Decrease in pancreatic and gallbladder secretion
[UpToDate: PP has a number of inhibitory actions that are believed to be important for both pancreatic and gastrointestinal function. Because many of its actions are local, it has been difficult to assess the magnitude of PP’s effects in the pancreas; however, it is well recognized to inhibit pancreatic exocrine secretion. In addition, PP has inhibitory effects on gallbladder contraction and gut motility, and may influence food intake, energy metabolism, and the expression of gastric ghrelin and hypothalamic peptides. PYY inhibits vagally stimulated gastric acid secretion and other motor and secretory functions. PYY-producing cells of the ileum are stimulated by incompletely digested nutrients, particularly fats. PYY released into the bloodstream can inhibit several gastrointestinal processes, including gastric emptying and intestinal motility, thus delaying the delivery of additional food to the intestine. This concept is known as the “ileal brake” and is believed to be mediated largely by PYY. Like PP, PYY also signals to the brain to reduce food intake by acting on Y2 receptors in the hypothalamus. In the periphery, PYY induces lipolysis and improves glycemic control by increasing insulin sensitivity through a reduction in circulating fatty acids.]
What is the body’s response to Vasoactive intestinal peptide (VIP) secretion?
- Increased intestinal secretion of water and electrolytes
- Increased intestinal motility
[UpToDate: Vasoactive intestinal polypeptide (VIP) is an important neurotransmitter throughout the central and peripheral nervous systems. Due to its wide distribution, VIP has effects on many organ systems. In particular, it:
- Stimulates gastrointestinal epithelial secretion and absorption
- Promotes fluid and bicarbonate secretion from bile duct cholangiocytes
- Is a potent relaxer of smooth muscle, including the lower esophageal sphincter and colon
- Increases the growth of certain adenocarcinomas
- Causes vasodilation
- Exerts anti-inflammatory actions
VIP, along with nitric oxide, is a primary component of the non-adrenergic non-cholinergic nerve transmission in the gut. Gastrointestinal smooth muscle exhibits a basal tone, or sustained tension, which is generated by rhythmic depolarizations (also called slow waves) of the smooth muscle membrane. Contractions occur when the slow waves reach a threshold level for calcium entry through calcium channels. VIP serves as an inhibitory transmitter of this rhythmic activity, causing membrane hyperpolarization and subsequent relaxation of gastrointestinal smooth muscle. In the intestine, VIP neurons project not only to other enteric neurons but also to muscle and epithelial cells, where they regulate circular muscle and epithelial chloride secretion.
VIP is an important neuromodulator in sphincters of the gastrointestinal tract including the lower esophageal sphincter and sphincter of Oddi. In certain pathological conditions, such as achalasia and Hirschsprung disease, the lack of VIP innervation is believed to have a major role in defective esophageal relaxation and bowel dysmotility.
VIP has immunomodulatory properties. It is produced by a population of Th2 lymphocytes and promotes Th2-type immune responses. In antigen-primed CD4 T cells in vitro, VIP inhibits Th1 cytokines interferon gamma and IL-2. In macrophages and dendritic cells, VIP induces Th2 cytokines IL-4 and IL-5. In vivo, VIP administration increases the ratio of Th2/Th1 cells. VIP also downregulates TNF-alpha expression. Thus, VIP appears to regulate the balance between pro-inflammatory and anti-inflammatory influences by inducing the emergence of T-cell effectors. As a result, VIP has endogenous anti-inflammatory activity. Beneficial effects of VIP have been demonstrated in animal models of arthritis, sepsis, and pancreatitis. Considerable evidence suggests that VIP may participate in the pathogenesis of inflammatory bowel disease. These effects are likely due to its anti-inflammatory effects, but VIP also appears to regulate intestinal epithelial barrier function through effects on tight junction proteins. Although reports suggested that VIP could reduce the histopathological severity in an experimental model of colitis, these results have not been uniformly reproduced.
VIP has effects on pulmonary vasculature and may play a role in pulmonary arterial hypertension. VIP has been shown to relax pulmonary vascular smooth muscle and attenuate vasoconstriction induced by endothelin and other mediators. These actions likely contribute to the observation that mice with targeted disruption of the VIP gene have a phenotype that is remarkably similar to spontaneous pulmonary arterial hypertension with vascular remodeling and lung inflammation. The antiproliferative effects of VIP may limit pulmonary vascular remodeling, and VIP is being investigated as a possible treatment for pulmonary arterial hypertension.]
What inhibits secretin secretion?
- pH greater than 4.0
- Gastrin
[UpToDate: The major physiological actions of secretin are stimulation of pancreatic fluid and bicarbonate secretion. Bicarbonate, upon reaching the duodenum, neutralizes gastric acid and raises the duodenal pH, thereby “turning off” secretin release via a negative feedback mechanism. It has been suggested that acid-stimulated secretin release is regulated by an endogenous intestinal secretin-releasing factor (SRF). This peptide stimulates secretin until the flow of pancreatic proteases is sufficient to degrade the releasing factor and terminate secretin release. Confirmation of this negative feedback pathway awaits identification of the putative SRF.]
Which cells are the target of gastrin?
- Parietal cells
- Chief cells
[UpToDate: Gastrin is a primary physiologic mediator of gastric acid secretion. The human stomach secretes approximately 2 to 3 liters of acid-rich fluid per day. The regulation of acid secretion is influenced by the central, peripheral, and enteric nervous systems and multiple chemical messengers including gastrin, histamine, somatostatin, and acetylcholine.
The major cellular determinants of acid secretion involve the antral gastrin-secreting G cell, the enterochromaffin-like (ECL) cell of the stomach that secretes histamine, and the somatostatin-secreting D cell. The acid-secreting parietal cell possesses receptors for acetylcholine, histamine, and gastrin. Although activation of all three of these receptors can stimulate acid secretion, the most important mechanism of acid release occurs via stimulation of the ECL cell to secrete histamine, which in turn stimulates the parietal cell. The ECL cell receives stimulatory signals from gastrin and inhibitory signals from somatostatin. Somatostatin also provides inhibitory signals to antral G cells.
The CCK2 receptor can be found on pancreatic islet cells, and hypergastrinemia has been associated with islet cell hyperplasia and enhanced insulin secretion. In animals, coadministration of gastrin and glucagon-like peptide-1 can restore normoglycemia in diabetic mice, suggesting that gastrin may have incretin-like effects.]
What is the body’s response to secretin secretion?
- Increased pancreatic HCO3 release
- Inhibits gastrin release (this is reversed in patients with gastrinoma)
- Inhibits HCl release
[UpToDate: Although the primary action of secretin is to produce pancreatic fluid and bicarbonate secretion, it is also an enterogastrone (a substance that is released by ingested fat and inhibits gastric acid secretion). In physiological concentrations, secretin inhibits gastric acid release, gastric motility, and gastrin release. When studied using pharmacologic doses, secretin also increases bile flow, gastrointestinal motility, and lower esophageal sphincter pressure, and stimulates insulin release following the ingestion of glucose.
Many studies suggest that secretin can promote growth of the pancreas. This latter finding has raised speculation that secretin may contribute to pancreatic cancer. However, direct evidence for secretin in the pathogenesis of pancreatic cancer is currently lacking. Interestingly, targeted ablation (knockout) of secretin-producing cells in transgenic mice resulted in an animal devoid of many enteroendocrine cells, suggesting that secretin expression may be necessary at an early step in the development of gut endocrine cells.
Like several other gut peptides, secretin has anorectic properties when administered centrally or peripherally. The central effects of secretin on satiety are mediated by the melanocortin system. The satiety-inducing effects of peripherally administered secretin are blocked by vagotomy or ablating sensory nerves with capsaicin, indicating that secretin signals through the sensory fibers of the vagus nerve. Although the satiety effects of secretin are relatively weak compared with other gut peptides such as cholecystokinin or peptide YY, its action on the vagus nerve highlights the importance of this neural pathway in regulating signals from the gut to the brain.
The physiological role of secretin in the brain is incompletely understood, although it may act as a neuropeptide. Impaired synaptic plasticity and antisocial behavior has been observed in secretin-receptor-deficient mice. During development, secretin has neurotrophic effects on serotoninergic mesencephalic neurons, and these effects are lost in neurodegenerative diseases.]
Where is gastrin produced?
Stomach antrum
[UpToDate: The vast majority of gastrin is produced in endocrine cells of the gastric antrum (G cells). Much smaller amounts of gastrin are produced in other regions of the gastrointestinal tract including the nonantral stomach, duodenum, jejunum, ileum, and pancreas. Gastrin has also been found outside of the gastrointestinal tract including the brain, adrenal glands, respiratory tract, and reproductive organs, although its biological role in these sites is unknown.]
Which cells produce gastrin?
G cells of the stomach
[UpToDate: Gastrin is released from specialized endocrine cells (G cells) into the circulation in response to a meal. The G cells are tightly regulated by two counterbalancing hormones, gastrin-releasing peptide and somatostatin, which exert stimulatory and inhibitory effects, respectively.]
Where is motilin produced?
Intestine (especially the duodenum and jejunum)
[Motilin is secreted by endocrine M cells that are numerous in crypts of the small intestine, especially in the duodenum and jejunum.]
[Wikipedia: Motilin is secreted by endocrine M cells (these are not the same M cells that are in Peyer’s patches) that are numerous in crypts of the small intestine, especially in the duodenum and jejunum. It is released into the general circulation in humans at about 100-min intervals during the inter-digestive state and is the most important factor in controlling the inter-digestive migrating contractions; and it also stimulates endogenous release of the endocrine pancreas. Based on amino acid sequence, motilin is unrelated to other hormones. Because of its ability to stimulate gastric activity, it was named “motilin”. Apart from in humans, the motilin receptor has been identified in the gastrointestinal tracts of pigs, rats, cows, and cats, and in the central nervous system of rabbits.]
What is the body’s response to cholecystokinin (CCK) secretion?
- Increased pancreatic enzyme secretion
- Gallbladder contraction
- Relaxation of the sphincter of Oddi
[UpToDate: Cholecystokinin (CCK) is the primary hormone responsible for gallbladder contraction. Coincident with stimulating gallbladder contraction, CCK also relaxes the sphincter of Oddi, which facilitates bile secretion into the intestine. Although CCK is a potent stimulant of pancreatic exocrine secretion in most species, the predominant CCK receptor type in the pancreas in humans is CCK2, which has a much higher affinity for gastrin than for CCK. As a result, CCK may have a limited role as a pancreatic secretagogue in humans. On the other hand, CCK receptors are present on the vagus nerve and appear to mediate the effects of CCK on pancreatic secretion by causing the release of acetylcholine locally in the pancreas. CCK may have weak incretin action. Experimentally in humans, CCK was shown to potentiate amino acid-stimulated insulin secretion and in patients with type II diabetes, CCK infusion-enhanced insulin release, and reduced postprandial glucose levels.
Gastric emptying is delayed by CCK, which may be one mechanism by which CCK can reduce food intake and induce satiety. The effects of CCK on the stomach appear to occur with physiologic postprandial blood levels of the hormone. Since CCK levels increase after ingestion of a meal, its effects on gallbladder contraction, pancreatic secretion, and gastric emptying serve to coordinate many digestive processes. Thus, CCK is a key regulator of the ingestion and digestion of a meal.
CCK acts on vagal afferent nerve fibers and sends signals to the dorsal hindbrain to terminate meal size and increasing the intermeal interval. Administration of CCK antagonists to animals and humans increases food intake by increasing meal size. Continuous administration of CCK to animals reduces food intake but this effect is lost after 24 hours. However, a long-acting CCK analog resistant to enzyme degradation produced sustained food reduction in non-human primates.]
Where is peptide YY produced?
Terminal ileum
[UpToDate: Peptide YY (PYY) has been localized to enteroendocrine cells in the mucosa of the gastrointestinal tract and is most highly concentrated in the ileum and colon. PYY is produced by two different cell types within the intestine, namely, L cells where it is colocalized with enteroglucagon and H cells of the colon and rectum. It has long been held that enteroendocrine cells are elongated or “flask”-shaped cells that reside in the intestinal mucosa with their apical surface open to the lumen of the intestine. In this position, enteroendocrine cells can “sense” luminal contents such as food or bacteria. Stimulation of cells causes the release of hormones from the basal surface into the paracellular space, where they are taken up by blood vessels and carried to distant sites of action. However, a new concept for enteroendocrine cell function is now apparent with the discovery that PYY cells possess neuropods that extend from their basal surface. Neuropods contain many features typical of neurons, including synaptic boutons, neurofilaments, pre- and post-synaptic proteins, and small, clear synaptic vesicles. Moreover, it has been discovered that enteroendocrine cells connect directly with enteric nerves [14]. This new epithelial-neural circuit provides a pathway for the gut to connect directly to the brain. It is possible that this pathway is involved in how the brain senses gut contents.
Which antibiotic is a motilin agonist?
Erythromycin
[UpToDate: Erythromycin, a motilin agonist, induces high-amplitude gastric propulsive contractions that increase gastric emptying. Erythromycin also stimulates fundic contractility, or at least inhibits the accommodation response of the proximal stomach after food ingestion. Patients who fail to respond to a trial of metoclopramide and domperidone should be treated with oral erythromycin (liquid formulation, 40 to 250 mg three times daily before meals).
Oral erythromycin should be administered for no longer than four weeks at a time, as the effect of erythromycin decreases due to tachyphylaxis. Use of higher doses (eg, 250 mg, compared with 40 mg) may be more likely to cause abdominal pain or induce tachyphylaxis. Chronic administration of oral erythromycin should be restricted to patients who have failed to respond to other prokinetics and who continue to demonstrate an improvement in symptoms over baseline and tolerance of oral feeding. Intravenous erythromycin should be reserved for acute exacerbations of gastroparesis in which oral intake is not tolerated.
Intravenous erythromycin significantly improves gastric emptying. Although gastric emptying is also improved with oral erythromycin, this improvement is smaller as compared with intravenous administration. In a systematic review of five clinical trials involving oral erythromycin for gastroparesis, 26 of 60 patients (43%) had an improvement in symptoms of gastroparesis. However, the studies included were small (≤13 subjects), of short duration (≤4 weeks), and had methodologic limitations.
Tachyphylaxis to erythromycin and potential side effects limit its use in the management of gastroparesis. Side effects of erythromycin include gastrointestinal toxicity, ototoxicity, the induction of resistant bacterial strains, QT prolongation, and sudden death, particularly when used in patients taking medications that inhibit CYP3A4.]
Which cells produce insulin?
Beta cells
[UpToDate: Insulin is a 51-amino acid peptide hormone that is synthesized and secreted by pancreatic beta cells. Pancreatic beta cells are found in the islets of Langerhans, which are of various size and contain a few hundred to a few thousand endocrine cells. Islets are anatomically and functionally separate from pancreatic exocrine tissue (which secretes pancreatic enzymes and fluid directly into ducts that drain into the duodenum). Normal subjects have about one million islets that in total weigh 1 to 2 grams and constitute 1-2% of the mass of the pancreas.
Islets vary in size from 50 to 300 micrometers in diameter. They are composed of several types of cells. At least 70% are beta cells, which are localized in the core of the islet. These cells are surrounded by alpha cells that secrete glucagon, smaller numbers of delta cells that secrete somatostatin, and PP cells that secrete pancreatic polypeptide. All of the cells communicate with each other through extracellular spaces and through gap junctions. This arrangement allows cellular products secreted from one cell type to influence the function of downstream cells. As an example, insulin secreted from beta cells suppresses glucagon secreted from alpha cells.
A neurovascular bundle containing arterioles and sympathetic and parasympathetic nerves enters each islet through the central core of beta cells. The arterioles branch to form capillaries that pass between the cells to the periphery of the islet and then enter the portal venous circulation.]
Which cells produce cholecystokinin (CCK)?
I cells of the duodenum
[UpToDate: Cholecystokinin (CCK)-containing cells (known as I cells) are concentrated in the proximal small intestine and decrease in number toward the distal jejunum and ileum. CCK cells originate from stem cells in the intestinal crypts and migrate up the villus, where the apical surface is exposed to intestinal contents. CCK cells possess basal processes that extend to other cells in the mucosa and submucosa. It is possible that through this mechanism CCK cells communicate with neighboring cells to exert paracrine actions.]
Where is pancreatic polypeptide produced?
Head of the pancreas
[Pancreatic polypeptide is produced by PP cells in the endocrine pancreas predominantly in the head of the pancreas.]
[UpToDate: The pancreatic polypeptide (PP) family of peptides functions as endocrine, paracrine, and neurocrine transmitters. Neuropeptide Y (NPY) is a true neurotransmitter, being released from nerve terminals, while peptide YY (PYY) and PP are hormones acting in both a paracrine and endocrine manner. Following a meal, PP is released into the blood from PP cells of the pancreas via vagal-cholinergic stimulation. PP concentrations also fluctuate with the myoelectric activity of the gastrointestinal tract. Plasma PP levels increase in phase with the periodic contraction and secretion of the gut, an effect that is abolished with ganglionic blockade. There is growing evidence that gut microbiota influence the nervous system, and it is likely that this occurs through release of hormones such as PYY or through the enteroendocrine cell-neuronal connection described above.
In contrast to PP, PYY levels change very slowly and not to the same degree in response to a meal. Moreover, PYY release does not depend upon intact vagal input. Meal-stimulated PYY release in humans occurs primarily in response to ingested fat, primarily short-chain and polyunsaturated fatty acids. Gastrointestinal diseases that cause malabsorption increase blood levels of PYY. In addition, surgical conditions that increase the delivery of food to the distal ileum and colon including small bowel resection, vertical band gastroplasty, Roux-en-Y gastric bypass, and jejunoileal bypass also elevate circulating PYY levels. G protein-coupled receptor 119 (GPR119) agonists have been shown to stimulate PYY release (along with glucagon-like peptide 1 and glucose-dependent insulinotropic peptide), indicating that GPR119 may be directly involved in hormone secretion.]
What are 4 the inhibitors of gastrin secretion?
- pH less than 3.0
- Somatostatin
- Secretin
- Cholecystokinin
[UpToDate: The specific components of a meal that stimulate gastrin release include protein, peptides, and amino acids. Gastrin release is profoundly influenced by the pH of the stomach; fasting and increased gastric acid in the stomach inhibit its release, whereas a high gastric pH provides a strong stimulus for its secretion. The G cells are tightly regulated by two counterbalancing hormones, gastrin-releasing peptide and somatostatin, which exert stimulatory and inhibitory effects, respectively.
Physiological regulation of gastrin secretion is highest when nutrients are in direct contact with G cells. Consequently, diversion of food from the antrum of the stomach, as with Roux-en-Y gastric bypass, has been associated with low blood levels of gastrin.]
What stimulates secretin secretion?
- Fat
- Bile
- pH less than 4.0
[UpToDate: The major physiological actions of secretin are stimulation of pancreatic fluid and bicarbonate secretion. Bicarbonate, upon reaching the duodenum, neutralizes gastric acid and raises the duodenal pH, thereby “turning off” secretin release via a negative feedback mechanism. It has been suggested that acid-stimulated secretin release is regulated by an endogenous intestinal secretin-releasing factor (SRF). This peptide stimulates secretin until the flow of pancreatic proteases is sufficient to degrade the releasing factor and terminate secretin release. Confirmation of this negative feedback pathway awaits identification of the putative SRF.]
Where is insulin produced?
Pancreas
[UpToDate: Insulin is a 51-amino acid peptide hormone that is synthesized and secreted by pancreatic beta cells. Pancreatic beta cells are found in the islets of Langerhans, which are of various size and contain a few hundred to a few thousand endocrine cells. Islets are anatomically and functionally separate from pancreatic exocrine tissue (which secretes pancreatic enzymes and fluid directly into ducts that drain into the duodenum). Normal subjects have about one million islets that in total weigh 1 to 2 grams and constitute 1-2% of the mass of the pancreas.
Islets vary in size from 50 to 300 micrometers in diameter. They are composed of several types of cells. At least 70% are beta cells, which are localized in the core of the islet. These cells are surrounded by alpha cells that secrete glucagon, smaller numbers of delta cells that secrete somatostatin, and PP cells that secrete pancreatic polypeptide. All of the cells communicate with each other through extracellular spaces and through gap junctions. This arrangement allows cellular products secreted from one cell type to influence the function of downstream cells. As an example, insulin secreted from beta cells suppresses glucagon secreted from alpha cells.
A neurovascular bundle containing arterioles and sympathetic and parasympathetic nerves enters each islet through the central core of beta cells. The arterioles branch to form capillaries that pass between the cells to the periphery of the islet and then enter the portal venous circulation.]
Where is cholecystokinin (CCK) produced?
Duodenum
[UpToDate: Cholecystokinin (CCK)-containing cells (known as I cells) are concentrated in the proximal small intestine and decrease in number toward the distal jejunum and ileum. CCK cells originate from stem cells in the intestinal crypts and migrate up the villus, where the apical surface is exposed to intestinal contents. CCK cells possess basal processes that extend to other cells in the mucosa and submucosa. It is possible that through this mechanism CCK cells communicate with neighboring cells to exert paracrine actions.
CCK is a member of the family of “brain-gut” peptides in which the same transmitter is found in the intestine and central nervous system. Although CCK is found in neurons throughout the brain, it is most highly concentrated in the cerebral cortex. CCK has been colocalized in neurons containing dopamine. These neurons project to the limbic forebrain and ventromedial hypothalamus, which may be important for regulating food intake. It has been suggested that CCK has an important role in the regulation of satiety.
CCK is also abundant in peripheral nerves of the gastrointestinal tract, which innervate the colon, ileum, and myenteric and submucosal plexus, and in the celiac plexus and vagus nerve. Although the exact physiologic actions of CCK in the nervous system are unknown, it most likely functions as a neurotransmitter.]
What is the body’s response to peptide YY secretion?
- Inhibits acid secretion
- Inhibits stomach contraction
- Inhibits gallbladder contraction
- Inhibits pancreatic secretion
[UpToDate: PP has a number of inhibitory actions that are believed to be important for both pancreatic and gastrointestinal function. Because many of its actions are local, it has been difficult to assess the magnitude of PP’s effects in the pancreas; however, it is well recognized to inhibit pancreatic exocrine secretion. In addition, PP has inhibitory effects on gallbladder contraction and gut motility, and may influence food intake, energy metabolism, and the expression of gastric ghrelin and hypothalamic peptides. PYY inhibits vagally stimulated gastric acid secretion and other motor and secretory functions. PYY-producing cells of the ileum are stimulated by incompletely digested nutrients, particularly fats. PYY released into the bloodstream can inhibit several gastrointestinal processes, including gastric emptying and intestinal motility, thus delaying the delivery of additional food to the intestine. This concept is known as the “ileal brake” and is believed to be mediated largely by PYY. Like PP, PYY also signals to the brain to reduce food intake by acting on Y2 receptors in the hypothalamus. In the periphery, PYY induces lipolysis and improves glycemic control by increasing insulin sensitivity through a reduction in circulating fatty acids.]
What stimulates cholecystokinin (CCK) secretion?
- Amino acids
- Fatty acid chains
[UpToDate: As with most gastrointestinal hormones, cholecystokinin (CCK) is secreted in response to ingestion of a meal, after which plasma concentrations increase approximately 5-to-10-fold. Postprandial levels remain elevated for 3-5 hours while food empties from the stomach into the upper small intestine. The primary stimulants of CCK release are ingested fat and protein; carbohydrates have a less potent effect on secretion.
The release of CCK is controlled by negative feedback regulation. This concept arose from studies demonstrating that inactivation or removal of proteolytic activity from the small intestine of rodents resulted in increased pancreatic exocrine secretion. Similar findings have been made in other species, including humans, whereby pancreatic secretion is controlled in part by the presence or absence of pancreatic enzymes (eg, trypsin) in the intestine.
This observation led to the discovery in animals of intestinal releasing factors that are secreted into the intestine and stimulate CCK secretion. These releasing factors are inactivated by pancreatic enzymes in the intestine. However, they are able to stimulate CCK secretion when pancreatic secretion is reduced or with ingestion of a meal that temporarily binds trypsin and other digestive enzymes. Whether these releasing factors are present in humans remains unclear.]
What inhibits glucagon secretion?
- Increase in blood glucose
- Increase in insulin
- Somatostatin
Which cells produce pancreatic polypeptide?
PP or F cells
[Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells (islet cells) in the endocrine pancreas predominantly in the head of the pancreas.]
What stimulates glucagon secretion?
- Decrease in blood glucose
- Increase in amino acids
- Acetylcholine
Somatostatin is mainly produced by which cell type?
D (delta) cells in the pyloric antrum of the stomach, the duodenum and the pancreatic islets
[UpToDate: Somatostatin is produced by paracrine and endocrine-like D cells and by enteric nerves. Somatostatin cells are morphologically diverse. In the gut mucosa, D-cells are flask-shaped and contain long cytoplasmic extensions that end in nerve terminal-like processes poised to participate in endocrine regulation either via release into the systemic circulation or direct secretion onto a neighboring cell. These cells appear uniquely suited to sample the luminal contents and influence local cell responses in a paracrine manner. In the central and peripheral nervous systems, nerves release somatostatin where it functions as a peptidergic neurotransmitter.]
Where is somatostatin produced?
- Stomach antrum
- Duodenum
- Pancreas
[UpToDate: Somatostatin is distributed throughout the entire body, although it is particularly abundant in nervous tissue of the cortex, hypothalamus, brainstem, and spinal cord. It has also been localized in nerves of the heart, thyroid, skin, eye, and thymus. Somatostatin is abundant in the gastrointestinal tract and pancreas where it is produced by paracrine and endocrine-like D cells and by enteric nerves. Both S-14 and S-28 are expressed throughout regions of the gastrointestinal tract.
Somatostatin cells are morphologically diverse. In the gut mucosa, D-cells are flask-shaped and contain long cytoplasmic extensions that end in nerve terminal-like processes poised to participate in endocrine regulation either via release into the systemic circulation or direct secretion onto a neighboring cell. These cells appear uniquely suited to sample the luminal contents and influence local cell responses in a paracrine manner. In the central and peripheral nervous systems, nerves release somatostatin where it functions as a peptidergic neurotransmitter.]
Where is secretin produced?
Duodenum
[UpToDate: Immunocytochemistry has demonstrated that secretin-producing cells are found along the small intestine. Other sites shown to produce secretin mRNA include the hypothalamus, cortex, cerebellum, and brainstem.]
What are the 6 stimulators of gastrin secretion?
- Amino acids
- Vagal input (acetylcholine)
- Calcium
- Ethanol
- Antral distention
- pH greater than 3.0
[UpToDate: The specific components of a meal that stimulate gastrin release include protein, peptides, and amino acids. Gastrin release is profoundly influenced by the pH of the stomach; fasting and increased gastric acid in the stomach inhibit its release, whereas a high gastric pH provides a strong stimulus for its secretion. The G cells are tightly regulated by two counterbalancing hormones, gastrin-releasing peptide and somatostatin, which exert stimulatory and inhibitory effects, respectively.
Physiological regulation of gastrin secretion is highest when nutrients are in direct contact with G cells. Consequently, diversion of food from the antrum of the stomach, as with Roux-en-Y gastric bypass, has been associated with low blood levels of gastrin.]
What is the body’s response to somatostatin secretion?
- Inhibits the release of gastrin
- Inhibits the release of HCl
- Inhibits the release of insulin
- Inhibits the release of glucagon
- Inhibits the release of secretin
- Inhibits the release of Motilin
- Decreases pancreatic and biliary output
[UpToDate: The physiological effects of somatostatin are largely inhibitory. In the peripheral organs, somatostatin decreases endocrine and exocrine secretion and blood flow, reduces gastrointestinal motility and gallbladder contraction, and inhibits secretion of most gastrointestinal hormones. Somatostatin also inhibits neurotransmission in the brain, but depending on the neural pathways affected, somatostatin in the central nervous system may stimulate endocrine secretion. For example, somatostatin inhibits ghrelin release from X/A-like cells of the gastric mucosa, but in the brain, somatostatin receptor activation increases plasma ghrelin levels.
Excess somatostatin secretion is rare and occurs with somatostatinomas. The clinical syndrome is manifest by the triad of (i) diabetes mellitus, (ii) diarrhea secondary to malabsorption, and (iii) gallstone disease. These pathophysiologic processes are the direct result of the inhibitory effects of somatostatin on insulin secretion, pancreatic exocrine secretion, and gallbladder contraction, respectively.]
