phys 51- GI hormones

actions of GIP

Actions of GIP Increases Insulin Release Inhibits Gastric motility Inhibits Gastric acid secretion Produced by K-cells of the duodenum and jejunum One of two "Incretins" GIP slows gastric motility GIP increases insulin release from pancreas GIP metabolized by Dipeptidyl peptidase -4 (DPP4) Food touches duodenum K cells make GIP Makes food absorb slower Helps control diabetes Can increase GIP by blocking its digestion

effects of gastrin

Actions of Gastrin Acid (H+) secretion from parietal cell- huge gradient Gastric lining growth )trophic effect) Increases Gastric motility

action of secretin

Actions of Secretin Pancreatic Bicarbonate Production & Release Biliary Bicarbonate Production & Release Gastrin Inhibition Production Inhibits gastrin Effect on parietal cells Increases pancreas growth Inhibits gastric emptying Increases insulin level Secretin causes bicarb release from pancreas Acts like activating a bicarb sprinkler system Most common place for ulcers is first part of duodenum where all the acid goes Lipase needs a basic pH to work- so the acid must be neutralized- fat stimulates CCK which secretes bile, but fat also stimulates secretin which decreases pH so that lipase will function Secretin shuts off gastrin- this slows GI motility Which increases insulin most IV or oral glucose- oral because you get the GI hormones reacting

stimuli for Glucose dependent insulinotropic peptide GIP

Also call "Gastric Inhibitory Peptide" (GIP) Stimuli for Secretion Carbohydrates Amino Acids Fatty Acids Also called .... Food!!! Because of this homology, pharmaco- logic levels of GIP produce most of the actions of secretin. GIP is secreted by K cells of the duodenal and jejunal mucosa It is the only gastrointestinal hormone that is secreted in response to all three types of nutrients: glucose, amino acids, and fatty acids. Carbohydrates stimulate GIP the most It increases insulin

glucagon like peptide

Bad Name! Glucagon "like" peptide (GLP) is NOT like glucagon! Inhibits Glucagon Lowers Glucose levels Increases insulin level Grows the pancrease Increases the sensitivity of pancreatic beta cells to secretagogues such as glucose Inhibs appetite Genetically speaking it comes from the same peptide as glucagon, but it actually inhibits it It is synthesized and secreted by the L cells of the small intestine. Like GIP, GLP-1 is classified as an incretin

Q7. Which of the following is stimulated most by fat? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

CCK

what kind of molecules can be GI peptides

Can be..... Hormones or.. Neurocrines or.. Paracrines They control..... Contraction & Relaxation of Gut Enzyme secretion

effect of CCK

Causes gallbadder action CCK stimulates the release of bile Fat absorbing hormone Gallbladder contraction Sphincter of Oddi relaxation- sphincter at gallbladder Growth of pancreas and gallbladder Pancreatic enzyme release- remember it stims more than just enzymes of fat digestion Lipase Amylase Trypsin Bicarbonate & Insulin production Inhibits Gastric Emptying- which provides a sense of satisfaction because stomach is full Slows GI motility

function of the cells in the gastric pits and glands

Cells that make pepsinogen Cells that make acid Cells that make mucous protect from acid Pepsinogen is inactive

cushings disease

Cushings disease- when you make cortisol but you still have a high ACTH- it should be shut off

name the 3 DPP4 inhibitors again

DPP4 inhibitors are: Sitagliptin Saxagliptin Linaglip they are added on to other drugs for treatment of diabetes Genuvia is the brand name it's the number 2 used Metformin is number one diabetes medication They basically squeeze insulin out of the pancreas Incretins increase the insulin

characteristics of synthetic GLP

Exenatide Liraglutide Subcutaneous injection Last 12 hours instead of 1-2 minutes extracted from lizard saliva

Q4. Which of the following increases insulin levels the most? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

GIP

Q8. Which of the following is degraded by dipeptidyl dipeptidase-4? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

GIP

function of GLP

GLP will: Slow gastric motility- makes it easier for pancreas to handle Decrease acid production Treat diabetes Also called an "incretin" Also metabolized by Dipeptidyl peptidase -4 (DPP4) Made by "L" cells in small intestine Short half life (1-2 minutes) Therapeutic for diabetes!! Increased by the DPP4 inhibitors Sita, Saxa and Linagliptin!!

which is the only GI hormone that has feedback inhibition

Gastrin Feedback Inhibition Acid (H+) suppresses gastrin

gastrinoma

Gastrinoma- is a failure in the feedback inhibitiion leading to inappropriate production of gastrin= zollenger-ellisons disease

histamine

Histamine is secreted by endocrine-type cells of the gastrointestinal mucosa, particularly in the H+- secreting region of the stomach. Histamine, along with gastrin and ACh, stimulates H+ secretion by the gastric parietal cells. potentiates acid

Q12. Which of the following explains the etiology of diarrhea in Zollinger-Ellison syndrome? (gastrinoma) Acid is an osmotic cathartic Gastrin increases colonic motility Inhibition of cholecystokinin Inhibition of Secretin Inactivation of lipase

Inactivation of lipase

how do you increase GIP

Increasing GIP can treat diabetes! Inhibiting Dipeptidyl peptidase -4 (DPP4) treats diabetes DPP4 inhibitors are: Sitagliptin Saxagliptin Linaglip NEED TO KNOW THESE NAMES

insulinoma

Insulinoma- when you make a lot of insulin but your blood sugar is still low

pathogenesis of ulcers

NSAIDS inhibit mucus Stretch makes the gastrin gastrin makes the acid Acids makes pepsinogen Pepsin makes an ulcer Prostoglandins make the mucous Stretch makes the protstoglandins So the same stimuli that makes the acid makes the mucous

which stimulates insulin more IV glucose or oral glucose

Oral glu- cose stimulates GIP secretion, which stimulates insulin secretion (in addition to the direct stimulatory action of absorbed glucose on the β cells). Glucose given intravenously stimulates insulin secretion only by the direct action on the β cells GIP is an incretin= insulin stimulating hormone

is pepsin necessary

Pepsin is not necessary for life!!- most freq asked question

GI neurocrines

Peptides synthesized in neurons of GI tract Released by an actin potential Acetylcholine (Ach) Norepinephrine Vasoactive intestinal Peptide (VIP) Gastrin-Releasing Peptide (GRP)

GI peptide hormones

Released by GI tract cells GI hormone cells not in glands Pass through portal blood and liver and back to target Gastrin Cholecystokinin (CCK) Secretin Gastric inhibitory peptide or Glucose-dependent insulinotropic peptide (GIP) Hormones in other places are secreted by glands like thyroid etc, but in GI they come from G cells or S cells that are scattered evenly around the GI tract. It has just as much secretion as these other endochrine glands Hormones are peptides released from endocrine cells of the gastrointestinal tract. They are secreted into the portal circulation, pass through the liver, and enter the systemic circulation. The systemic circulation then delivers the hormone to target cells with receptors for that hormone which could be in the GI tract or elsewhere in the body

Q11. A patient presents with ulcers that recur despite eradication of H. pylori with a proton pump inhibitor (PPI) and two antibiotics. There is a high gastrin level and a high gastric acid output. Which of the following is most useful to establish a diagnosis? Rise in gastrin after IV secretin Cessation of acid when restarting PPI Failure of H2 blocker Urea Breath testing

Rise in gastrin after IV secretin

GI paracrines

Secreted by GI endocrine cells Paracrines act locally Diffuse short distances Somatostatin is an inhibitory peptide Histamine is paracrine but is not a peptide Somatostatin inhibits almost everything Inhibits acid production Inhibits release of growth hormone Inhibits insulin release Inhibits glucagon Enterochromaffin tissie- soomething between neural and glandular tissue, not quite either

functional part of secretin

Secretin, a 27-amino acid peptide, is structurally homol- ogous to glucagon Unlike gastrin and CCK the whole peptide is needed for function. It must fold into an alpha helix Secretin is secreted by the S cells (secretin cells) of the duodenum

somatostatin

Somatostatin is secreted by D cells (both endocrine and paracrine) of the gastrointestinal mucosa in re- sponse to decreased luminal pH. In turn, somatostatin inhibits secretion of the other gastrointestinal hor- mones and inhibits gastric H+ secretion. In addition to these paracrine functions in the gastrointestinal tract, somatostatin is secreted by the hypothalamus and by the delta (δ) cells of the endocrine pancreas. it inhibits like everything

gastrin - stimuli for secretion

Stimuli for Secretion Distention of Stomach (stretch) Protein "parts"-AAs, peptides phenylalanine and tryptophan are the most potent stimuli for gastrin secretion Vagal stimulation (Ach) Gastrin releasing peptide (GRP) released from nerves onto G cells The greatest stimulant to gastrin is stratch of the stomach from eating or hunger

stimuli for secretin

Stimuli for Secretion (Release) Acid (H+) in duodenum Fatty acids in duodenum thus, secretion of secretin is initiated when the acidic gastric contents (pH < 4.5) arrive in the small intestine.

stimuli for cholecysteokinin

Stimuli for Secretion of CCK Fat in duodenum (NOT TGA's) Monoglycerides Free fatty acids Protein Parts (AAs and Peptides)

gastrin peptide during a meal and between meals

The 17-amino acid form of gastrin, which is called G17 or "little" gastrin, is the form of gastrin secreted in response to a meal. A 34-amino acid form of gastrin, which is called G34 or "big" gastrin, is secreted during the interdigestive period between meals each form of gastrin has its own bio- synthetic pathway, beginning with its own precursor, a progastrin molecule. Only need the C terminal tetrapeptide for basic gastrin function

the functional part of CCK

The C-terminal five amino acids (CCK-5) are identical to those of gastrin and include the tetrapeptide that is minimally necessary for gastrin activity. Thus, CCK has some gastrin activity The minimum fragment of CCK necessary for its biologic activity is the C-terminal heptapeptide (seven amino acids [CCK-7]). Secreted by I cells of dudenal and jejunal mucosa

what are the names of the 2 incretins

There are 2 incretins GIP and GLP GLP inhibits glucagon and raises insulin Both GIP and GLP are metabolized by DPP4

pheochromocytoma

When you make Norepi but your blood pressure is high pheochromocytoma

TSH adenoma

When you make a lot of thyroxin but your pituitary still make a lot of PTSH- TSh producing adenoma

zollinger-ellison syndrome

Zollinger-Ellison syndrome is caused by a gastrin- secreting tumor or gastrinoma, usually in the non-β-cell pancreas. The signs and symptoms of Zollinger-Ellison syndrome all are attributable to high circulating levels of gastrin: increased H+ se- cretion by parietal cells, hypertrophy of the gastric mucosa (the trophic effect of gastrin), and duodenal ulcers caused by the unrelenting secretion of H+. The increased H+ secretion also results in acidifica- tion of the intestinal lumen, which inactivates pan- creatic lipase, an enzyme necessary for fat digestion. As a result, dietary fats are not adequately digested or absorbed, and fat is excreted in the stool (steatorrhea). Treatment of Zollinger-Ellison syn- drome includes administration of H2 receptor- blocking drugs (e.g., cimetidine); administration of inhibitors of the H+ pump (e.g., omeprazole); removal of the tumor; or, as the last resort, gastric resection, which removes gastrin's target tissue.

Q9. Which of the following is the major stimulant to the release of gastrin? Fatty Acids Bicarbonate Distention Somatostatin Secretin

distention aka stretching

Q1. Which of the following is the only GI hormones to have feedback inhibition? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

gastrin

Q2. Which of the following is the only GI hormones to have neural stimulation? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

gastrin

Q3. Which of the following is the only GI hormones to increase gastric motility? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

gastrin

what inhibits gastrin

gastrin secretion is inhibited by a low pH of the gastric contents and by somatostatin. note he said Acid stimulates pepsin which breaks down proteins ..the Aas stimulate gastrin

Q10. A patient presents with epigastric pain. Upper endoscopy shows a duodenal ulcer. She is placed on omeprazole. Two days later the gastrin level is found to be elevated. What best explains this? Failure to use antibiotics Zolinger-Ellison syndrome Helicobacter pylori Loss of feedback inhibition Lack of efficacy of omeprazole

loss of feed back inhibition

Q6. Which of the following is inhibited by food? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

motilin

Q5. Which of the following is stimulated most by acid? Cholecystokinin Secretin Gastrin GIP (glucose insulinotropic peptide) Motilin

secretin

paracrines

somatostatin histamine

summary table of GI hormones

table