The Gut as an Endocrine Organ Flashcards
What are some characteristics of a hormone?
Endocrine, paracrin and autocrine signalling (not juxtacrine)
Soluble factor
Stimulus-secretion coupling
Precursor cleavage
Short half-life
What is the first hormone discovered and its role?
Secretin
Secreted by duodenal S-cells in response to increased acidity
Controls gut pH by stimulating bicarbonate releaes from exocine pancreas = inhibiting gastric acid release from parietal cells of stomach
What manner is secretin secreted?
Endocrine manner = via blood
What is the mechanism of pancreatic secretion?
Secretion of pancreatic juice = normally evoked by enterance of acid chyme into duodenum
Contact of acid with epithelial cells of duodenum = causes secretin to be secreted
Secretin carried by blood to pancreas = pancreatic juice proportional to amount of acid entering
This secretion does not depend on nervous reflex = occurs when all nervous connection of intestine are destroyed
Which pathway are homrones secreted via?
Regulated secretory pathway
Simulus-secretion coupling mechanism
Some hormones can be secreted via constituitive pathway (exosomes)
What are the 6 functions of the gut?
Digestion
Absorption
Excretion
Motility (maintain flux)
Immunity
Secretion (digestive enzymes & hormones)
What is different between the small intestine and large intestine?
Small has villi and crypts
Large only has crypts
What does the lamina propria consist of?
Blood vessels
Nerve endings
Immune cells
All required for normal gut physiology and host defence
What receptors do gut hormones generally bind?
G-protein coupled receptors on target cells
What do the X/A cells of the GIT secrete?
Ghrelin = orexigenic
Only hormones that stimulates HUNGER
Regulated by fasting
What do the G-cells of the GIT secrete?
Gastrin = gastric acid release from parietal cells
Mechanical, vagal and nutrient regulated
What do the S-cells of the GIT secrete?
Secretin = stimulates bicarbonate release from pancreas
pH regulated
What do the I-cells of the GIT secrete?
Cholecystokinin (CCK) = stimulates bile release from gall bladder and digestive enzymes from pancreas
Nutrient regulated
What do the K-cells of the GIT secrete?
Glucose-dependent insulinotropic peptide (GIP) = potentiates insulin secretion from endocrine pancreas
Nutrient regulated
What do the L-cells of the GIT secrete?
GLP-1
Peptie YY = satiety signal
Oxyntomodulin = satiety signal
What is a characteristic of endocrine cells?
Cell population are NOT discrete
Most cells can secrete more than one hormone = hybrid
What other factors affect beta-cells?
Fre fatty acids
Amino acids
Circulating horones
ACh from SNS
Doesn’t only respond to glucose = integrates various signals form body and secrete appropriate amounts of insulin
What is the incretin effect?
Insulin secretion is greater in response to ORAL glucose intake copmared to i.v infusion
Where is glucagon-like peptide (GLP-1) derived from?
The proglucagon gene, which can code for multiple hormones
What is the role of GLP1 in insulin secretion?
GLP1 POTENTIATES insulin secretion
BUT
Does NOT sitmulate insulin secretion in the absence of a depolarising stimulus (glucose)
How does GLP-1 act on alpha-cells?
Directly acts on alpha-cells
e
Enhancing paracrine
inhibition of glucagon release
Where does GLP-1 act in the CNS?
Hypothalamus = arcuate nucleus and paraventricular nucleus
Directly and via vagal afferent nerves projecting to the NTS
What does GLP-1 regulate in the CNS?
REgulates feeding behaviour, energy metabolism and the cardiovascular system
What is serum GLP1 activity regualted by?
DppIV degrades GLP-1 = causing its short serum half-life (minutes)
How does GLP-1 promote beta-cell proliferation?***
Via GPCR = second messenger cAMP
What is the issue with GLP-1 as a therapeutic agent?
Has a short-half life so would need to be infused a long time to sustain elevated GLP-1 conc in serum
So GLP-1 analgues created have been made to evade degredation by DPPIV
OR
Use DPPIV inhibitors to stabilise endogenous GLP1 in serum
What receptor does pepetide YY act on and what is its affect?
Activates Y2 recepotr
Suppreses food intake via direct effect on HYPOTHALAMUS (humoural pathway) and via vagal afferents (neural pathway)
What effect does manipulating the incretin effect with bariatric surgery have?
Restoration of glucose homeostasis occurs = even before weight loss
This is potentiall because of the shorted stomach so nutrient-stimulation reaches L-cells quicker
