Lec 14 - Gut hormones Flashcards
2 types of enteroendocrine cells (EEC)
- open EEC = has microvilli to sample the lumen
- closed EEC = no access to lumen, recieve input from eihter blood or neurotransmitters from motor neurons
what do EECs do
release hormones in response to nutrints in gut lumen
what type of hromone are most GI hromones
peptides that bind to GPCRs
3 types of gut peptide hromones
- gastrins = regulate digestive process
- secretins = induce hormone release
- motilins = regulate gastric motility
the 3 phases of hromone release
- cephalic phase
- gastric phase
- intestinal phase
Cholecystokinin (CCK): where released from
I cells in duodenum
Cholecystokinin (CCK): when released
stimulated by fat and protein in intestinal lumen
Cholecystokinin (CCK): what receptor
CCK 1 receptor
Cholecystokinin (CCK): effects
decreased gastric motility
delayed gastric emptying
increased satiety (smaller meals BUT eat more frq, so food intake is acc the same = not used to treat obesity)
Glucose dependent insulinotropic polypeptide (GIP): wehre released from
K-cells in duodenum
Glucose dependent insulinotropic polypeptide (GIP): released why
stimulated by sugar and fat
Glucose dependent insulinotropic polypeptide (GIP): effects
Incretin horome release to increase insulin secretion from pancreatic beta cells
Glucose dependent insulinotropic polypeptide (GIP): what type of hormone
endocrine
Glucose dependent insulinotropic polypeptide (GIP): where does it act
on GIPR on beta cells in pancreas
- GIPR also throughout the body
Glucose dependent insulinotropic polypeptide (GIP): why doesnt it reduce food intake on its own effectively
doesnt reach the CNS cuz degraded so fast
Glucose dependent insulinotropic polypeptide (GIP): what do long acting GIPRA allow
long acting GIP agonists
allow bidning to GIPR in brainstem = reduce food intake and body weight
Glucagon like peptide-1 (GLP-1): where released
L - cells in ileum and jejunum
Glucagon like peptide-1 (GLP-1): when released
- in cephalic phase = stimulated by neural input from brain
- post-prandially is stimulated by sugar
Glucagon like peptide-1 (GLP-1): effects
- an incretin hromone: inc insulin release
- decreases glucagon release
- ileal brake = inhibit gastric emptying,
Glucagon like peptide-1 (GLP-1): what type of hromone
endrocrine and neural
Glucagon like peptide-1 (GLP-1): what does it do in the CNS
acts on ARC and AP to increase satiety
Glucagon like peptide-1 (GLP-1): what receptor
GLP-1R
Glucagon like peptide-1 (GLP-1): effects on vagal afferent neurons
triggers vago-vagal reflex
decreases gastric emptying
increases satiation
enzyme that cleaves GLP-1, giving it a short half life
DPP4
what are gliptins
DPP-4 inhibitors = inc circulating GLP-1
what are exendins
analogues of GLP-1 that are resistant to DPP4
primary fucntion of leptin
signals sufficiency of adipose stores to permit various biological functions
leptin deficiency symptoms
obese
hyperphagic
leptin receptor>
LepR
5 types, located peripherallly and centrally
receptor tyrosine kinases
what does receptor tyrosine kinases trigger
JAK/STAT signalling pathways
Leptin: what type of signalling
neural and endocrine
how does leptin affect orexigenic and anorexignic signals
- attenuates orex
- potentiates anorex
= induces satiety
effect of circulating leptin binding to LepR in arcuate nucleus
- inhibits AgRP/NPY
- stimulates POMC neurons = release of aMSH
= reduced food intake
= increased energy expendature
what might hyperleptinaemia lead to
leptin resistance
leptin resistancce as a cause of obesity
rare
but can have congenital defect in leptin gene
OR
leptin receptor defects
Ghrelin: released from where
- Pd1 cells in stomach
- X/A cells in enteroendocrine
- episilon cells in islets of langerhans literally wtf is that
Ghrelin: when stimulated
cephalic phase
empty stomach is major trigger for ghrelin
Ghrelin: main function
the only HUNGER hormone
appetite stimulus
increases gastric motility
increases gastric acid secretion
Ghrelin: effects of adminstering exogenous ghrelin
stim feelings of hunger
causes hunger pains, by contracting gi tract muscles
Ghrelin: how does it signal
neural and endocrine pathways
Ghrelin: what receptor
growth hormone secretagogue receptor (GHSR)
Ghrelin: where are GHSR
either:
- vagal/sympathetic afferent neurons (neural)
- target tissues e.g. brain (endocrine)
how does leptin control ghrelin
High adiposity = high leptin = inhibition of ghrelin = decreases hunger
And vice versa
Ghrelin: in terms of endorcrine control, what does it act on
the GHSR in arcuate nucleus:
- stimulates AgRP/NPY neurones
- inhibits POMC neurons
