Gut Hormones (7-8) Flashcards
What are some features of gut hormones?
→ all peptide hormones
→ many found elsewhere (e.g. brain)
→ act in both paracrine and endocrine fashion
What are some hormones of the upper gut/stomach?
Ghrelin → hunger, growth hormone releasing
Gastrin → acid secretion
What are some hormones of the middle gut/duodenum?
Secretin → pancreatic exocrine secretion
GIP → incretin activity
Motilin → gastrointestinal motility
What is the gross anatomy of the GI tract?
GI = gastrointestinal
→ a long continuous muscular digestive tube
involved in: ingestion, propulsion, mechanical digestion, chemical digestion, absorption, defecation
What are some functional considerations of the GI tract?
→ substances in the GI tract lumen are outside of the body
→ multiple sensors and receptors line the GI tract to monitor contents and respond to conditions
→ controls: intrinsic (local control) and extrinsic (CNS)
What are the four tunics of the GI tract?
Mucosa → epithelium, lamina propria, muscular mucosae
Submucosa → glands, receptors
Muscularis externa → longitudinal muscle, circular muscle
Serosa → epithelium, connective tissue
Does the innermost mucosa differ throughout the GI tract?
The histology/morphology is slightly different throughout
→ oesophagus, stomach, small intestine, large intestine differ - functional diversity
→ same tunics are there
→ e.g. small intestine - more absorpative
Where are the endocrine cells found?
Gastric pits in the stomach lining
→ gastric pits lead to gastric glands
Cells in gastric gland change as you go down
→ mucous cells, parietal cells, chief cells and enteroendocrine cells
What is the function of parietal cells?
Produce HCL
→ maintain acidic environment for proper digestion and nutrient absorption
→ controlled by enteroendocrine cells
→ acidity changes biology of Na H+ pumps
What is the function of chief cells?
Role in secreting enzyme pepsinogen
→ becomes active form pepsin in acidic environment
What is the function of enteroendocrine cells?
Paracrine
Neuronal → afferent vagal, splanchnic and enteric nerves
Endocrine → enters blood
Regulates digestive and metabolic functions, appetite and energy homeostasis
What are 7TM chemosenesors?
G-protein couples receptors found on entero-endocrine cells in the GI tract
→ have 7 transmembrane domains
→ involved in detecting luminal contents - nutrients, metabolites etc
e.g. short chain fatty acids → GPR41
proteolytic products → GPR93
bile acids → GPR131
activation causes release of GI-tract hormones
What are G-cell endocrine cells?
Type of endocrine cell found in stomach responsible for releasing gastrin
Food enters stomach
→ signals in pit to G cell
→ G cells sense increase Ca2+
→ release gastrin
→ gastrin regulates parietal cells
→ release of HCl
regulate gastric acid secretion and maintaining digestive function
How does gastrin work?
Controls acid secretion directly → via CCK receptors on parietal cells
Control acid secretion indirectly → through inducing histamine containing ECL cells
Regulated by pH and somatostatin
Also drives mucosal growth and effects gastric motility
What signals to parietal cells?
Parietal cells have many signals - lots of things controlling them
→ direct from gastrin
→ histamine from ECL
→ neural input
→ feedback via somatostatin from D cells
How is the movement of membrane and vesicles regulated in parietal cells?
Primarily driven by the action of proton pumps and transporters in the cell membrane
Proton pump → H+ out of cytoplasm, K+ into cytoplasm contributing to the acidic environment
Chloride ions → Cl out of cytoplasm into stomach lumen following gradient established by proton pumps
Fusion of vesicles leads to secretion of HCl
Regulated by hormones like gastrin, somatostatin and histamine
What are proton pump inhibitors?
Used for indigestion, peptic uncles and increased acid secretion
e.g. omeprazole
massive industry
How do parietal cells regulate vitamin B12 absorption?
Parietal cells secrete intrinsic factor
→ glycoprotein hormone required for vitamin B12 absorption in the ilium
Loss of parietal cells can lead to pernicious anaemia (changes avg volume of RBC)
How is gastrin synthesised?
Gastrin gene transcribed and translated in G cell nucleus - forms preprogastrin (precursor of gastrin)
Preprogastrin undergoes post-translational modifications as it moves through ER → signal peptide removed forming progastrin
Further processing produces mature gastrin peptides - gastrin34gly, gastrin34, gastrin17
Stored in secretory vesicles in G cells
Metabolised by kidney, intestine and liver
How is somatostatin regulated in the stomach?
Low gastric pH stimulates delta cells (found in antrum where they are open to the lumen) that secrete somatostatin and inhibit gastrin release
Also influenced by
→ mechanical stimulation
→ dietary components of a meal
→ other hormones and neurotransmitters
What are the functions of somatostatin?
In the gut somatostatin has broad inhibitory action
→ reduces gastric acid production
→ reduces pepsinogen secretion (form chief cells)
→ inhibits pancreatic enzyme, fluid and bicarbonate secretion
→ reduces bile flow
→ inhibits gut motility
→ reduces intestinal transport of nutrients and fluid
→ inhibits tissue growth and proliferation
What is Zollinger-Ellison syndrome?
Gastrin secreting tumours in the pancreas/duodenum
→ excessive secretion of gastrin - stimulates stomach acid production
→ results in severe peptic ulcers
How is glucose controlled after a meal?
Stimulation of insulin secretion from pancreatic beta cells
Inhibition of hepatic gluconeogenesis by suppression of glucagon secretion
Delaying delivery of carbohydrates to the small intestine by inhibiting gastric emptying
What is the entero-insular axis?
The communication pathway between the entero-endocrine cells in the GI tract and the pancreas
→ allows for coordinated regulation insulin and glucagon secretion in response to changing nutrient availability
→ 50% of insulin release driven by GI hormones called incretins e.g. GLP-1, GIP
