GI Hormones Flashcards
enteroendocrine cells (EECs)
specialized cells in the GI tract that secrete GI hormones in response to specific luminal, endocrine, and neural signals
source (cell type) for gastrin
G cells
location of G cells
*gastric antrum (stomach)
*duodenum
note - G cells secrete gastrin
stimulus for secretion of gastrin
*amino acids & peptides
*gastric distension
inhibitors of gastrin production
*H+ (acid; via somatostatin)
*secretin
target of gastrin
parietal cells (promotes release of stomach acid)
actions of gastrin
- increases gastric acid secretion (stimulates enterochromaffin-like cells, which release histamine and cause parietal cells to release gastric acid)
- increases growth of gastric mucosa
- increases gastric motility
gastrinoma
*aka Zollinger-Ellison (ZE) Syndrome
*uncontrolled gastrin secretion → excess gastric acid hypersecretion
*presents with abdominal pain, heartburn, steatorrhea, weight loss
*positive secretin stimulation test (increased gastrin levels after secretin administration, which normally inhibits gastrin release)
Zollinger-Ellison (ZE) Syndrome
*neoplastic G-cells
*uncontrolled gastrin secretion, leading to very high plasma levels
*drives very high gastric acid output
*causes severe peptic ulceration of stomach, duodenum, and small intestine
*causes watery diarrhea and steatorrhea (fatty diarrhea)
*tx: surgical resection; octreotide
source (cell type) for secretin
S cells
location of S cells
*duodenum
note - S cells make secretin
stimulus for secretion of secretin
*H+ (pH < 4.5)
*fatty acids
inhibitors of secretin production
*pH > 4.5 (PPIs, H2-blockers)
targets of secretin
*pancreas
*bile ducts
*stomach
secretin in the clinic
*used diagnostically to test for ZE syndrome
*secretin inhibits gastrin secretion from NORMAL G cells
*BUT, paradoxically, secretin STIMULATES gastrin secretion from gastrin-producing EEC tumors in ZE syndrome
actions of secretin
*INCREASED pancreatic & biliary bicarbonate (HCO3-) secretion
*DECREASED gastric acid secretion
*DECREASED gastric motility
*(+) pancreatic cell growth
source (cell type) for CCK
I-cells
location of I-cells
*duodenum
note - I cells make CCK
stimulus for secretion of CCK
*fatty acids
*amino acids
inhibitors of CCK production
*bile acids
targets of CCK
*CCK-1 receptors in:
-gallbladder
-pancreas
-stomach
-smooth muscle
-nerves
actions of CCK
*INCREASED GALLBLADDER CONTRACTION
*INCREASED BILE SECRETION
*INCREASED PANCREATIC ENZYMES
*decreased gastric emptying & acid
* (+) induces satiety via vagus
CCK in the clinic
*CCK can be used for evaluating gallbladder function:
-synthetic CCK is used in radiology to evaluate gallbladder function (contractility)
source (cell type) for motilin
M-cells
location of M-cells
*duodenum
note - M cells make motilin
stimulus for secretion of motilin
*neural control
inhibitors for production of motilin
food ingestion
target of motilin
motilin receptors on GI tract smooth muscle cells
actions of motilin
*plasma levels oscillate during inter-digestive period
*activates the migrating myoelectric complex (MMC)
migrating myoelectric complex (MMC)
cycles of electrical and motor activity** which migrate from the gastric antrum to the ileum every ~90 min
**clears lumen to prepare for next meal
*maintains SB zone of relative sterility
*ACTIVATED by MOTILIN
motilin in the clinic
*used to treat gastroparesis
*erythromycin is an “accidental” ligand for the motilin receptor & causes abdominal side effects
*erythromycin used as a PRO-MOTILITY agent for treatment of gastroparesis
*highly specific motilin receptor agonists are being developed to treat dysmotility syndromes
“Incretin Effect”
*ORAL glucose stimulates MORE insulin secretion than IV glucose
-mediated by hormones secreted from proximal gut (GIP) and distal gut (GLP-1) in response to nutrients
*incretins are rapidly deactivated by the plasma enzyme DPP-4
acronym for GLP-1
glucagon-like peptide-1
note - GLP-1 is an incretin hormone
source (cell type) for GLP-1
L cells
location of L cells
*ileum
*colon
note - L cells make GLP-1
stimulus for secretion of GLP-1
*carbs
*amino acids
*fatty acids
inactivation of GLP-1 (and other incretins)
DPP-4 (half life < 2 min)
targets of GLP-1
*beta cells
*liver
*gastric smooth muscle
*CNS
*heart
actions of GLP-1
INCREASED INSULIN SECRETION** & decreased glucagon secretion
**decreased gastric emptying
* (+) satiety via CNS
*other effects on heart, liver, skeletal muscle
use of GLP-1 to treat diabetes
1) GLP-1 agonists that are RESISTANT to DPP-4 (such that the GLP-1 is not rapidly inactivated by DPP-4) [ex. Ozempic]
2) DPP-4 inhibitors that prolong effects of ENDOGENOUS GLP-1
use of GLP-1 agonists to treat obesity
*ex. Tirzepatide
*synthesis of a composite molecule that combines GIP and GLP-1 compounds to inhibit appetite
source (cell type) for somatostatin
D cells
location of D cells
*stomach
*small bowel (SB)
*pancreas
note - D cells make somatostatin
somatostatin in the stomach
stomach: vagal stimulation: DECREASED secretion of somatostatin, leading to increased acid secretion
somatostatin in the pancreas
pancreas: vagal stimulation: INCREASED secretion of somatostatin, leading to decreased insulin secretion
targets of somatostatin
*EEC (enteroendocrine cells)
*smooth muscle
*pancreas
*pituitary
actions of somatostatin
*(-) ALL neuroendocrine cell secretion
*decreased insulin & glucagon secretion
*decreased gut and bile fluid secretion
*decreased GI motility
*decreased mesenteric blood flow
somatostatin in the clinic
*a synthetic somatostatin analog (octreotide) can be used for many reasons, including:
-ZE syndrome
-acromegaly
-severe uncontrolled diarrhea
-insulinoma
*most commonly used for: DIVERTICULAR HEMORRHAGE and variceal hemorrhage
source (cell type) for ghrelin
P/D1 cells
location of P/D1 cells
stomach
note - P/D1 cells make ghrelin
stimulus for secretion of ghrelin
fasting
inhibitors for production of ghrelin
food intake
target of ghrelin
receptors on gastric smooth muscle and CNS
actions of ghrelin
*STRONGLY OREXIGENIC (makes you hungry)
*plasma levels oscillate and peak before meals
*increased gastric motility
