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Endocrine Control of Endocrine Control of Gastrointestinal FunctionGastrointestinal Function
Dr.Mohammad ShaikhaniDr.Mohammad Shaikhani
Glucose, AAGlucose, AA
Fatty acidsFatty acids
DuodenumDuodenum
JejunumJejunum
Insulin secretion Insulin secretion
Gastric acid secretionGastric acid secretionGIPGIP
Acidfat
DuodenumDuodenum Pepsin secretion Pepsin secretion
Pancreatic juice secretion Pancreatic juice secretion
enzymesenzymes
bicarbonatebicarbonate
Pancreatic exocirne growthPancreatic exocirne growth
SecretinSecretin
Peptides, AAPeptides, AA
Fatty acids>8CFatty acids>8CAcidAcid
DuodenumDuodenum
JejunumJejunum
Gall Bladder contraction Gall Bladder contraction
Pancreatic juice secretion Pancreatic juice secretion
enzymeenzyme
bicarbonatebicarbonate
Pancreatic exocirne growthPancreatic exocirne growth
CCKCCK
Peptides, AAPeptides, AA
DistentionDistention
Vagal activityVagal activity
AntrumAntrumduodenumduodenum
Gastric acid secretion Gastric acid secretion
Growth of oxyntic gland Growth of oxyntic gland
mucosamucosa
GastrinGastrin
Secretion stimulusSecretion stimulusRelease siteRelease siteActionActionHormoneHormone
GI HormonesGI Hormones
Glucose
Fat
IleumIleum unknownunknownEnteroglucagonEnteroglucagon
ProteinProteinFatFat
GlucoseGlucose
PancreasPancreas Pancreatic juice secretion Pancreatic juice secretion
enzymeenzyme
bicarbonatebicarbonate
Pancreatic Pancreatic polypeptidepolypeptide
UnknownUnknownDuodenumDuodenum
JejunumJejunum
Gastric andGastric and
duodenal motilityduodenal motilityMotilinMotilin
SecretionSecretion
stimulusstimulus
Release siteRelease siteActionActionPeptidePeptide
GI HormonesGI Hormones
Gastric mucosaGastric mucosa
Muscosa and Muscosa and smooth muscle smooth muscle of GI tractof GI tract
Stimulates gastrin secretionStimulates gastrin secretion
Stimulates smooth muscle Stimulates smooth muscle contractioncontraction
Inhibits intestinal secretionInhibits intestinal secretion
Bombesin or GRPBombesin or GRP
EnkephalinsEnkephalins
DuodenumDuodenum
JejunumJejunum
Relaxes sphinctersRelaxes sphincters
Relaxes gut circular muscleRelaxes gut circular muscle
Stimulates intestinal secretionStimulates intestinal secretion
Simulates pancreatic Simulates pancreatic secretionsecretion
VIPVIP
Release siteRelease siteActionActionPeptidePeptide
NeurocrinesNeurocrines
Activation of pancreatic
proteases in small intestine
• CCK stimulates duodenal mucosal cells to produce enteropeptidase
Hormone secretions of small intestine: CCK
•Inhibits gastric emptying•↑ secretion of pancreatic enzymes &HCO3
-
•Stimulates release of enteropeptidase•Stimulates gall bladder contractions
Chyme with a:•High amino acid •High fatty acid •Low pH
Primarily duodenal mucosa
ActionsStimuli for secretionSite of secretion
CCK: most important stimulus
for gall bladder contraction &
release of bile into small intestine
Hormone secretions of the small intestine: secretin
•Inhibits gastric emptying•↑ secretion of pancreatic enzymes & HCO3
-
•Stimulates release of enteropeptidase
•Stimulates gall bladder contractions•↓ HCl production in stomach
•↑ biliary HCO3- secretion
Chyme with a:•High amino acid concentration•High fatty acid concentration•Low pH
Primarily duodenal mucosa
ActionsStimuli for secretion
Site of secretion
Hormone secretions of the small intestine: CCK
Cholecystokinin:"move the gallbladder“.Cholecystokinin:"move the gallbladder“.
Cholecystokinin plays a key role in facilitating digestion within the small intestineCholecystokinin plays a key role in facilitating digestion within the small intestine..
It is secreted from mucosal epithelial cells in the first segment of the small intestine It is secreted from mucosal epithelial cells in the first segment of the small intestine
(duodenum).(duodenum).
It is also produced by neurons in the It is also produced by neurons in the enteric nervous systementeric nervous system& widely distributed in & widely distributed in
the brain. the brain. It stimulates delivery into the small intestine of It stimulates delivery into the small intestine of digestive enzymes from the pancreasdigestive enzymes from the pancreas
& & bile from the gallbladderbile from the gallbladder. .
The most potent stimuli for secretion of cholecystokinin are the presence of partially-The most potent stimuli for secretion of cholecystokinin are the presence of partially-
digested fats & proteins in the lumen of the duodenum. digested fats & proteins in the lumen of the duodenum.
Disease StatesDisease States
Cholecystokinin deficiency causes malabsorption similar to pancreatic exocrine Cholecystokinin deficiency causes malabsorption similar to pancreatic exocrine
insufficiency. insufficiency.
In the human brain causes certain types of anxiety & schizophrenia.In the human brain causes certain types of anxiety & schizophrenia.
Hormone secretions of the small intestine: Gastrin
It is a major physiological regulator of gastric acid secretionIt is a major physiological regulator of gastric acid secretion
An important growth-promoting influence on the gastric mucosa. An important growth-promoting influence on the gastric mucosa.
Gastrin is synthesized in G cells, in the antrum of the Gastrin is synthesized in G cells, in the antrum of the stomachstomach , binds receptors found , binds receptors found
predominantly on predominantly on parietalparietal & & enterochromaffinenterochromaffin-like cells-like cells. .
Control and Physiologic Effects of GastrinControl and Physiologic Effects of Gastrin
The primary stimulus for secretion of gastrin is the presence of certain foods, The primary stimulus for secretion of gastrin is the presence of certain foods,
especially peptides, certain amino acids &calcium, in the gastric lumen&unidentified especially peptides, certain amino acids &calcium, in the gastric lumen&unidentified
compounds in coffee, wine, beer.compounds in coffee, wine, beer.
Secretion of this hormone is inhibited when the lumenal pH of the stomach becomes Secretion of this hormone is inhibited when the lumenal pH of the stomach becomes
very low (< 3). very low (< 3).
Disease StatesDisease States
Excessive secretion of gastrin, or hypergastrinemia, Occur in Zollinger-Ellison Excessive secretion of gastrin, or hypergastrinemia, Occur in Zollinger-Ellison
syndrome, result of gastrin-secreting tumors (gastrinomas), which develop in the syndrome, result of gastrin-secreting tumors (gastrinomas), which develop in the
pancreas or duodenumpancreas or duodenum with excessive &unregulated secretion of gastric acid with excessive &unregulated secretion of gastric acid causingcausing
intractable peptic ulceration.intractable peptic ulceration.
Hormone secretions of the small intestine: secretin
Secretin functions as a type of fireman:Secretin functions as a type of fireman:
it is released in response to acid in the small intestine& stimulates the pancreas to it is released in response to acid in the small intestine& stimulates the pancreas to
release of bicarbonate, which neutralizes the acid.release of bicarbonate, which neutralizes the acid.
A similar, but less important response to secretin is A similar, but less important response to secretin is bile duct cellsbile duct cells, resulting , resulting
in additional bicarbonate releases& pumped into the SI.in additional bicarbonate releases& pumped into the SI.
Hormone secretions of the small intestine: VIP
VIP is very widely distributed in the peripheral & central nervous VIP is very widely distributed in the peripheral & central nervous
systems, & GI. systems, & GI.
VIP induce smooth muscle relaxation (lower esophageal sphincter, VIP induce smooth muscle relaxation (lower esophageal sphincter,
stomach, gallbladder).stomach, gallbladder).
Stimulate secretion of water into pancreatic juice & bile& cause inhibition Stimulate secretion of water into pancreatic juice & bile& cause inhibition
of gastric acid secretion & absorption from the intestinal lumen. of gastric acid secretion & absorption from the intestinal lumen.
Certain tumors from the pancreatic islets or nervous tissue (called Certain tumors from the pancreatic islets or nervous tissue (called
VIPomas) secrete excessive quantities of VIP& are associated with chronic, VIPomas) secrete excessive quantities of VIP& are associated with chronic,
watery diarrhea.watery diarrhea.
Hormone secretions of the small intestine: Motilin
Motilin secreted by endocrinocytes in the mucosa of the proximal small intestine. Motilin secreted by endocrinocytes in the mucosa of the proximal small intestine.
Motilin controlsMotilin controls smooth muscle contractions in the upper GIT. smooth muscle contractions in the upper GIT.
Motilin is secreted into the circulation during the fasted state & sweep the stomach Motilin is secreted into the circulation during the fasted state & sweep the stomach
&small intestine clear of undigested material (&small intestine clear of undigested material (migrating motor complexmigrating motor complex). ).
An alkaline pH in the duodenum stimulates its release. An alkaline pH in the duodenum stimulates its release.
Erythromycin & related antibiotics act as nonpeptide motilin agonists& used for Erythromycin & related antibiotics act as nonpeptide motilin agonists& used for
their ability to stimulate GIT motility. their ability to stimulate GIT motility.
Hormone secretions of the small intestine: GIP
Gastric inhibitory peptide (GIP)Gastric inhibitory peptide (GIP)
or Glucagon-Like peptide(GLP)or Glucagon-Like peptide(GLP)
Or glucose-dependant insulinotropic peptideOr glucose-dependant insulinotropic peptide
Is a member of the secretin family of hormones. Is a member of the secretin family of hormones.
Inhibited gastric motility &secretion of acid, initially called Inhibited gastric motility &secretion of acid, initially called enterogastroneenterogastrone. .
Like secretin, it is secreted from mucosal epithelial cells in the first part of the small Like secretin, it is secreted from mucosal epithelial cells in the first part of the small
intestine. intestine.
Enhance the release of insulin in response to infusions of glucose (Enhance the release of insulin in response to infusions of glucose (glucose-dependent glucose-dependent
insulinotropic peptideinsulinotropic peptide))
Used as a base for treating diabetes melitus.Used as a base for treating diabetes melitus.
GLP-1: effects in humans
GLP-1 is secreted fromL-cells of the jejunum
and ileum
That in turn…
• Stimulates glucose- dependent insulin secretion
• Suppresses glucagonsecretion
• Slows gastric emptying
Long-term effectsin animal models:
• Increase of β-cell mass and improved β-cell function
• Improves insulin sensitivity
• Leads to a reduction offood intake
After food ingestion…
Drucker. Curr Pharm Des. 2001Drucker. Mol Endocrinol. 2003
Hormone secretions of the SI: Ghrelin Ghrelin
Ghrelin peptide hormone stimulates release of growth hormone from the anterior Ghrelin peptide hormone stimulates release of growth hormone from the anterior
pituitary. pituitary.
Along with several other hormones, has significant effects on appetite and energy Along with several other hormones, has significant effects on appetite and energy
balance. balance.
The predominant source of ghrelin is epithelial cells in the stomach.The predominant source of ghrelin is epithelial cells in the stomach.
Also present on the cells in the pituitary that secrete growth hormone & in the Also present on the cells in the pituitary that secrete growth hormone & in the
hypothalamus, heart& adipose tissuehypothalamus, heart& adipose tissue. .