Endocrine Control of Endocrine Control of Gastrointestinal FunctionGastrointestinal Function

Dr.Mohammad ShaikhaniDr.Mohammad Shaikhani

HormoneHormone ActionAction Release siteRelease site Secretion stimulusSecretion stimulus

GastrinGastrin Gastric acid secretion Gastric acid secretion

Growth of oxyntic gland Growth of oxyntic gland

mucosamucosa

AntrumAntrumduodenumduodenum

Peptides, AAPeptides, AA

DistentionDistention

Vagal activityVagal activity

CCKCCK Gall Bladder contraction Gall Bladder contraction

Pancreatic juice secretion Pancreatic juice secretion

enzymeenzyme

bicarbonatebicarbonate

Pancreatic exocirne growthPancreatic exocirne growth

DuodenumDuodenum

JejunumJejunum

Peptides, AAPeptides, AA

Fatty acids>8CFatty acids>8CAcidAcid

SecretinSecretin Pepsin secretion Pepsin secretion

Pancreatic juice secretion Pancreatic juice secretion

enzymesenzymes

bicarbonatebicarbonate

Pancreatic exocirne growthPancreatic exocirne growth

DuodenumDuodenum Acidfat

GIPGIP Insulin secretion Insulin secretion

Gastric acid secretionGastric acid secretionDuodenumDuodenum

JejunumJejunum

Glucose, AAGlucose, AA

Fatty acidsFatty acids

GI HormonesGI Hormones

PeptidePeptide ActionAction Release siteRelease site SecretionSecretion

stimulusstimulus

MotilinMotilin Gastric andGastric and

duodenal motilityduodenal motilityDuodenumDuodenum

JejunumJejunum

UnknownUnknown

Pancreatic Pancreatic polypeptidepolypeptide

Pancreatic juice secretion Pancreatic juice secretion

enzymeenzyme

bicarbonatebicarbonate

PancreasPancreas ProteinProteinFatFat

GlucoseGlucose

EnteroglucagonEnteroglucagon unknownunknown IleumIleum Glucose

Fat

GI HormonesGI Hormones

PeptidePeptide ActionAction Release siteRelease site

VIPVIP Relaxes sphinctersRelaxes sphincters

Relaxes gut circular muscleRelaxes gut circular muscle

Stimulates intestinal secretionStimulates intestinal secretion

Simulates pancreatic Simulates pancreatic secretionsecretion

DuodenumDuodenum

JejunumJejunum

Bombesin or GRPBombesin or GRP

EnkephalinsEnkephalins

Stimulates gastrin secretionStimulates gastrin secretion

Stimulates smooth muscle Stimulates smooth muscle contractioncontraction

Inhibits intestinal secretionInhibits intestinal secretion

Gastric mucosaGastric mucosa

Muscosa and Muscosa and smooth muscle smooth muscle of GI tractof GI tract

NeurocrinesNeurocrines

Activation of pancreatic

proteases in small intestine

• CCK stimulates duodenal mucosal cells to produce enteropeptidase

Hormone secretions of small intestine: CCK

Site of secretion

Stimuli for secretion Actions

Primarily duodenal mucosa

Chyme with a:

•High amino acid

•High fatty acid

•Low pH

•Inhibits gastric emptying

•↑ secretion of pancreatic enzymes &HCO3

-

•Stimulates release of enteropeptidase

•Stimulates gall bladder contractions

CCK: most important stimulus

for gall bladder contraction &

release of bile into small intestine

Hormone secretions of the small intestine: secretin

Site of secretion

Stimuli for secretion

Actions

Primarily duodenal mucosa

Chyme with a:

•High amino acid concentration

•High fatty acid concentration

•Low pH

•Inhibits gastric emptying

•↑ secretion of pancreatic enzymes & HCO3

-

•Stimulates release of enteropeptidase

•Stimulates gall bladder contractions

•↓ HCl production in stomach

•↑ biliary HCO3- 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 enteric nervous system& widely distributed in It is also produced by neurons in the enteric nervous system& 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 pancreas & &

bile 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 stomach , binds receptors found Gastrin is synthesized in G cells, in the antrum of the stomach , binds receptors found

predominantly on parietal & enterochromaffin-like cells. predominantly on parietal & enterochromaffin-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 bile duct cells, resulting A similar, but less important response to secretin is bile duct cells, 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 (migrating motor complex). &small intestine clear of undigested material (migrating 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. .