Gastrointestinal Endocrine System

Submitted to: Dr. Shafaq FatimaSubmitted by: Sarwat Ishaq Course Title: Fish Endocrinology Class: MS-I (Maj/Zoology) Roll #: 3815523Lahore College for Women University, Lahore.

Gastrointestinal Endocrine System

Endocrine cells secrete hormones regulation of digestive processes i.e.nutrient absorptiongut motility intestinal blood flow

Definition:“Gastrointestinal endocrinology is the study of the hormonal regulation of digestion.”

gastrointestinal tract is subdivided

largest endocrine gland

(GIT) is not a mere site for the absorption

GIT and the endocrine system is multidirectional

Several peptides are synthesized and released

→ food intake→ energy metabolism→ endocrine balance

gastrointestinal endocrine cells

Gastrointestinal Endocrine System Gastroenteropancreatic endocrine cells

carbohydrate metabolism,

gastric acid secretion,

pancreatic exocrine

gallbladder function

By means of immunohistochemical and radioimmunochemical techniques

gastrointestinal endocrinology focused upon

gut-brain axis

Gut-derived peptides

food intake, before, during and after weight loss

Secretin, gastrin and cholecystokinin

Gastrointestinal Endocrine System

Hormone isolation and structure:small protein moleculeshormones are characterized

Polypeptide hormones in mammalian gastrointestinal endocrine cells

Gastrointestinal Endocrine System

The secretin family: Secretin, glucagon GHRH

The insulin family: Insulin, insulin-like growth factor I & II and relaxin

The gastrin family: Epidermal growth factor, transforming growth factor-a and amphiregulin.

The EGF family: Gastrin and cholecystokinin.

The PP-fold family: Pancreatic polypeptide

The tachykinin family:Substance P and neurokinins

The somatostatin family: Somatostatin and corticostatin

The peptide families:

Table 2- Characteristics of prominent forms of principal gut regulatory peptides:Hormone or peptide Molecular weight (Da) Number of amino acids Main gut localization Principal physiologic actions

Gastrin family

Cholecystokinin 3918 33 (also 385, 59)Duodenum and jejunum,

Enteric nerves

Stimulates gallbladder contraction and

intestinal motility; stimulates secretion

of pancreatic enzymes, insulin,

glucagon, and pancreatic polypeptides;

has a role in indicating satiety; the C-

terminal 8 amino acid peptide

cholecystokinin (CCK)-8 retains full

activity

Little gastrin 2098 17Both forms of gastrin are found

in the gastric antrum and

duodenum

Gastrins stimulate the secretion of

gastric acid, pepsinogen, intrinsic

factor, and secretin; stimulate intestinal

mucosal growth; increase gastric and

intestinal motilityBig gastrin 3839 34

Secretin-glucagon family

Secretin 3056 27 Duodenum and jejunum

Stimulates pancreatic secretion of

HCO3, enzymes and insulin; reduces

gastric and duodenal motility, inhibits

gastrin release and gastric acid

secretion

Vasoactive intestinal polypeptide

(VIP)

3326 28 Enteric nerves

Relaxes smooth muscle of gut, blood

vessels, and genitourinary system;

increases water and electrolyte

secretion from pancreas and gut;

releases hormones from pancreas, gut,

and hypothalamus

Glucose-dependent

insulinotropic4976 42 Duodenum and jejunum

Stimulates insulin release; reduces

gastric and intestinal motility;

increases fluid and electrolyte secretion

from small intestine

Gastrointestinal Endocrine System

Gut hormones as general messengers:

Hormone families can be assembled with regard to structural homologies.

The gut hormone genes are widely expressed

The hormone-producing cells can release their products The hormone genes

The same hormone gene can have a cell-specific expression

can express multiple bioactive peptides

Gastrointestinal Endocrine System

Gastro endocrinal system in FISH:

primary regulators of growth

food intake and endocrine function

largest endocrine gland

Secretion of hormones

ingested carbohydrates or amino acids

thyroid gland

evolutionarily-ancient characteristic

Gastrointestinal Endocrine System

Hormones of the Gut:

Peptides in nature 

Found in other tissues

act in a paracrine manner

importance to health

GASTRIN:

Edkins in 1906 when he discovered

gastric juice

major biological regulator of gut

initially released from the G cells

pancreatic endocrine cells, pituitary, and extra-antral G cells

The cellular targets for gastrin

key growth regulator

G-17 and G-34 amino acid peptides

biosynthetic pathways, progastrin-Gastrin

N- & C-terminal extensions removed by prohormone convertases

during fasting G-34 while after meal G-17

gastrin secretion from antral G cells is tightly regulated

Negative regulation of gastrin

 

Gastrointestinal Endocrine System

The interactions of the vagus affecting acid secretion and gastrin release.

H/KP

H/KP

histamine-secreting cell

Acetylcholine neural input neurocrine

Gastrin hormonal input

endocrine

PARIETAL cell

paracrine release of histamine

histamine receptor

ACh receptor

gastrin receptor

transduction-activation events

HClsecretion

Combined neurocrine, endocrine and paracrine events in the activation of gastric HCl secretion

ECL cell

G cellcirculation

ECL cell = enterochromaffin-like cell

G cell = gastrin-secreting cell

HOW IT WORKS AT THE RECEPTOR LEVEL

neural input

chemical input

Turning the G-cell On and Off

ACh ACh

ACh GRP

(Somatostatin)cell

(Gastrin)cellSS

GRPneuron

digestedprotein

H+

vagusnerve

CirculatingGastrin

GD+-

++

cholinergic neurongastric

mucosa

Gastric LumenGastric Lumen

Turning the G-cell On and Off

ACh ACh

ACh GRP

(Somatostatin)cell

(Gastrin)cellSS

GRPneuron

digestedproteinH+

vagusnerve

CirculatingGastrin

GD+

++

cholinergic neurongastric

mucosa

Gastric Lumen

SS = somatostatin

-

Integration of Gastric Secretion

+

+

++

+

+

Integration of Gastric Secretion

+ +

+

-

- -

+

++

+

+

Hormone Name Produced By Secreted By Method of

Stimulation Effect Notes (if applicable)

GastrinG cells in the antrum of the stomach, duodenum, and pancreas

G cells of the duodenum and in the pyloric antrum of the stomach

Distension; partially digested proteins, autonomic stimulation, ingestion of alcohol or caffeine – release inhibited by stomach pH of 2 (negative feedback) & somatostatin, secretin, gastroinhibitory peptide, vasoactive intestinal peptide, glucagon, calcitonin

Stimulates secretion of gastric acid (HCl) by the parietal cells in the stomach; causes a minor increase in gastric motility; stimulates parietal cell maturation & fundal growth; induces pancreatic secretions & gallbladder emptying

Peptide; found primarily in big (34), little (17), & mini (14) forms, with numbers referring to amino acid count. Optimum pH 5-7

Hormone Name Produced by Secreted by Method of

Stimulation Effects Notes (if applicable)

Gastric Inhibitory

Peptide (GIP)

K cells, found in the mucosa

of the duodenum and

jejunum

K cells, found in the mucosa

of the duodenum and

jejunum

n/a

Induces insulin secretion; has

significant effect on fatty

acid metabolism

Does NOT neutralize

stomach acid (that's

secretin); absence of GIP

receptors correlated with

resistance to obesity

Gastrointestinal Endocrine System

Cholecystokinin:

a member of the gut–brain family

endocrine cells located predominantly in the proximal small intestine as well as by the neurons in the brain

first described in 1928 by Ivy and Oldberg

CCK has been shown to be crucial for gallbladder contraction pancreatic enzyme secretion

inhibition of gastric emptying

potentiation of insulin secretion

CCK release is stimulated

binding to the receptor, intracellular calcium

pancreatic acinar cells and enzyme secretion

growth of the pancreas growth of GI mucosa

Regulation by CCK (Cholecystokinin)

CCK

gallbladder

Bile

FOOD

+

-

liver

+

fats & peptides

bile & enzymesfat &

protein digestion

- HCl

2. Duodenal Response to Food

Hormone Name Produced By Secreted By Method of

Stimulation Effect Notes (if applicable)

Cholecystokinin (CCK)

L-cells in the mucosal epithelium of the small intestine

Duodenum Fatty acids and peptides

Causes release of digestive enzymes and bile from the pancreas and gallbladder, respectively; slightly decreases gastric secretion; causes contraction of the gallbladder & relaxation of the hepatopancreatic ampullar sphincter; strongly decreases gastric motility; hunger suppressant

Induces drug tolerance to opioids and is implicated in the pain hypersensitivity during opioid withdrawal; peptide

Gastrointestinal Endocrine System

Gastrointestinal Endocrine System

D. Duodenal Integration & Control: 1. Response to Acidity

Regulation by Secretin

HCl + NaHCO3 NaCl + CO2 + H2O

+

+

-

+

gallbladder

liver

HCl

HClmotility

NaCl+ H2O

HCO3

HCl

NaHCO 3

NaHCO3

Secretin

Gastrointestinal Endocrine System

GHRELIN 28 AA:

relatively new member 1999

growth hormone secretagogue receptor (GHSR)

Source: gastric mucosa , Stomach, Small intestine & colon

Stimulate: Growth hormones from the pituitary active form : acyl ghrelin bind to GHSR-1a

Stimuli: fasting

Action: Act on hypothalamus to stimulate feeding

GHRELIN 28 AA:

• Action:

food intake,

energy homeostasis, gastric emptying

acid secretion

• Secretion

acetylcholine and gastric inhibitory peptide

CCK, SST, insulin

Conclusion:GIES regulates:

Food intake

Growth

Metabolism

Characterize an Appetite-regulating peptide

diversity of the fish group

Summary

References Larsson, L.I., Gruss, P. and St-Onge, L. 1998. Pax 4 and 6

regulate gastrointestinal endocrine cell development. Mechanisms of Development 79(1-2):153-159.

Gençer Tarakçi, B., Bayrakdar, A. and Yaman M. 2012. Immunohistochemical study of the endocrine cells in the stomach and pyloric caeca of the mountain trout, Salmo trutta macrostigma. Iranian Journal of Fisheries Sciences 11(4):776-785.

DİLER, D., ÇINAR, K. and ZORLU, S. 2011. An Immunohistochemical Study on the Endocrine Cells in the Stomach and Intestine Regions of the Dicentrarchus labrax, L., 1758. F.Ü.Sağ.Bil.Vet.Derg. 25 (1): 01 – 06.