Gastrointestinal hormones Flashcards
What do GI hormones regulate?
Feeling of hunger, motility, insulin release, secretion (of gastric acid, digestive enzymes)
Describe how most GI hormones begin as?
Larger precursors (often from same preprohormone product)
Why do GI hormones have short half life?
Inactivation and cleavage by peptidases (3-5mins)
Where are gut endocrine cells found?
Scattered in gut epithelium in crypts in villi
Describe structure of gut endocrine cells
Most have microvilli on apex opening to gut lumen (sense its contents)
Nutrient sensing apical GPCRs
What do gut endocrine cells sense/respond to?
Respond to carbs, bile salts lipids and proteins
From which surface of endocrine cells are gut hormones released?
Basally
What are the different routes for gut endocrine secretions?
Endocrine/paracrine, neuroendocrine (enteric nervous system)
What stimulates release of gut hormones?
Mechanical/electrical presence of food
Cephalic phase
What region(s) are hormones released from? What is the most common?
Stomach, duodenum, and colon
Small intestine is the most common
What mechanism releases peptide hormones?
Exocytosis
What layer are gut endocrine cells derived from?
Endoderm
What 2 structures release peptide hormones?
Gut endocrine cells
Nerves of ENS (endocrine)
Integrated role of gut endocrine and nervous systems…
Control motor/digestive/vascular activity of the gut
What are 2 families of gut hormones?
Gastrin like and secretin like
Example of gastrin like hormones
Gastrin, CCK
Example of secretin like hormones
VIP, secretin, GIP, glucagon
Which hormones regulate digestion (4)?
Histamine, somatostatin, secretin, gut glucagon
What hormone regulates digestion and appetite (1)?
CCK
What do the incretin hormones do, give an example?
Regulate insulin secretion
GIP and GLP1
Which hormones are released in stomach?
Histamine, gastrin, ghrelin and somatostatin
What hormone is released by duodenum?
Gastrin
What hormones are released by small intestine and colon?
VIP, CCK, PYY, GIP, GLP1
What cell makes histamine?
ECL cells of stomach
What is histamine made from, and how (enzyme)?
Histidine by histidine decarboxylase
What stimulates histamine release
Gastrin, vagal stimulation, and stretch
What are the actions of histamine?
Local paracrine action stimulate HCl secretion via H2 receptors on parietal cell
What receptor and what cell does histamine act on?
H2 receptor on parietal cells
Where is Gastrin synthesised?
G cells of gastric antrum crypts and duodenal cells
What factors stimulate gastrin secretion (4)?
Luminal protein digestion products (e.g. AA)
Vagus (via ACh + gastrin release peptide)
Stomach distention
Hypercalcaemia
What inhibits gastrin release?
Stomach pH<2.5 (H+ -ve feedback)
Somatostatin (and secretin)
What part of stomach makes gastrin?
Gastric antrum
What are the actions of gastrin (5)?
Stimulate gastric acid secretion via
insertion of K+/H+ ATPase into apical membrane of parietal cells
Parietal cell growth
Pepsinogen secretion secretion
Antral motility and mucosal blood flow
Water and electrolyte secretion in liver, pancreas and intestine
How does gastrin stimulate gastric acid secretion (2 ways)?
Directly via binding to parietal cell to induce apical expression of K+/H+ATPase
Indirectly binding to ECL cells to induce release of histamine (which acts on H2)
What receptor does gastrin bind to on parietal cells?
CCK-B
What are ECL cells?
Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell secreting histamine.
Where is secretin made?
From duodenum to ileum (S cells in the neck of crypts)
What cells secrete secretin?
S cells
Describe distribution of S cells from duodenum to distal ileum?
Fewer
What stimulates secretin release?
Acid in proximal duodenum
What inhibits secretin release?
Somatostatin
What are the effects of secretin?
Stimulate pancreatic secretions of HCO3- and water (wash pancreatic enzymes into gut)
Stimualte liver secretion of HCO3- and water into bile
(potentiate CCK, calcitonin PTH secretion)
Controlling gut pH
Reduces acid secretion by parietal cells of the stomach.
Which gut hormone is important for controlling gut pH?
Secretin
How does secretin reduce acid secretion by the stomach parietal cells?
Stimulating release of somatostatin
Inhibiting release of gastrin in the pyloric antrum
Direct downregulation of the parietal cell acid secretory mechanics.
What cells secrete somatostatin, where?
D cells in gastric antrum to colon
What is the function of somatostatin?
Suppresses secretion of GI hormones
Suppresses their effects (acid etc)
Retards absorption glucose (protects against post-prandial hyperglycaemia)
Where is VIP released?
Enteric neurons in pelvic parasympathetic nerves also in brain and in nerves in pancreas
What triggers VIP release
Unknown: not food releated
What triggers somastatin release?
Stimulated by meals: amino acids, glucose, fatty acids, gastrin, secretin.
What does VIP do?
Relaxes cardiac sphincter, stomach, anal sphincter; vasodilator. Causes pancreatic bicarbonate secretion.
What cells secrete motilin ?
Mo cells from antrum to colon
What is motilin thought to be involved with?
Initiating the MMC (migrating myoelectric motility complex)
What cells secret gut glucagon and where?
Gastric A cells
Ilial, colonic L cells
What effect does gut glucagon have?
Stimulates gastric/intestinal motility, stimulates intestinal absorption sugars, systemic glucagon-like effects.
Where is CCK made?
I cells in duodenum and jejunum
What stimulates release of CCK?
Protein and fat digestion products in duodenum
What are the actions of CCK (3)?
Stimulate secretion of pancreatic enzymes and potentiates secretin action
Contraction of gall bladder
Causes satiety by signalling on vagal afferent terminals
Which enzyme can potentiate secretin?
CCK
Which hormone stimulates gall bladder contraction and pancreatic enzyme secretion?
CCK
Which enzyme stimulates HCO3- excretion?
Secretin
What hormone stimulates pepsin and gastric acid secretion?
Gastrin
What releases GLP1?
L cells in small intestine
When is GLP1 released?
Meals, carbs, fat and GIP
What does GLP1 do?
Potentiates glucose stimulated insulin release (sensitises beta cells to glucose)
Suppresses appetite
What secrets GIP?
K cells small intestine
What does GIP do?
Potentiates glucose stimulates insulin release
What stimulates GIP production?
Oral, glucose, fat and protein
What hormone is important in gall bladder contraction?
CCK
What hormone is important in pancreatic enzyme secretion?
CCK
Where is CCK secreted from?
Duodenum
What is CCK secreted in response to?
Chyme in duodenum
