25 Gastrointestinal Peptides Chan Flashcards
What are the characteristics of Gut Peptide Hormones?
Diverse cellular sources. Wide scope of biological activities. Multiple structural forms. Multiple receptor subtypes. Multiple ligand-receptor specificity. Few therapeutic applications
What is Gastrin secreted by?
G cells in the stomach
What are the effects of Gastrin?
Increases acid secretion, increases mucus growth
What is the stimulus for Gastrin release?
Peptides and amino acids in lumen; Gastrin releasing peptide and ACh in nervous reflexes
What is Cholecystokinin (CCK) secreted by?
Endocrine cells of the small intestine (Duodenum/Jejunum); neurons of the brain and gut
What are the effects of Cholescystokinin (CCK)?
Stimulates pancreatic enzyme and HCO3 secretion. Stimulates bladder contractions; inhibits stomach emptying (promotes satiety)
What is the stimulus for Cholescystokinin (CCK) release?
Fatty Acids and some Amino Acids
What is Secretin secreted by?
Endocrine cells of the small intestine (Duodenum/Jejunum)
What are the effects of Secretin?
Stimulates pancreatic and hepatic HCO3 secretion; inhibits acid secretion; Pancreatic growth. Stimulates gallbladder contraction; inhibits stomach emptying
What is the stimulus for Secretin release?
Acid in small intestine
What is Gastric Inhibitory Peptide secreted by?
Endocrine K Cells of the small intestine
What are the effects of Gastric Inhibitory Peptide?
Stimulates pancreatic insulin release. Inhibits Acid secretion. Satiety and lipid metabolism
What is the stimulus for Gastric Inhibitory Peptide release?
Glucose, Fatty Acid, and Amino Acids in small intestine
What is Motilin secreted by?
Endocrine cells in the small intestine (Duodenum/Jejunum)
What are the effects of Motilin?
Stimulates migrating motor complex for motility
What is the stimulus for Motilin release?
Fasting: cyclic release every 1.5-2 hours by neural stimulus
What is Glucagon Like Peptide 1 secreted by?
Endocrine cells in small intestine
What are the effects of Glucagon Like Peptide 1?
Stimulates insulin release; inhibits glucagon release. Possibly inhibits acid secretion. Slows gastric emptying. Satiety
What is the stimulus for Glucagon Like Peptide 1 release?
Mixed meals of fats and carbohydrates
What secretes Somatostatin and where are they located?
D cells, located throughout the GI tract
Which GI regulatory peptide has endocrine, paracrine, neurocrine, and autocrine activity?
Somatostatin
Where are GI regulatory peptides with neurocrine activity secreted?
Synpatic cleft
How does Gastrin release regulate itself?
When released from G cells, Gastrin can act on the CCK2R on the D cell which releases Somatostatin. Somatostatin can then bind to SSTR2 on the G cell which inhibits further Gastrin release
Besides Gastrin release from the G cell, what else can stimulate Somatostatin release from the D cell?
ACh acting on the GRP nerve can activate the GRP receptor on D cells which causes Somatostatin release. This same nerve can also act on GRP receptors on G cells which can cause Gastrin release
How does Gastrin increase acid release?
Gastrin acts on CCK2R’s on Parietal cells which cause H+ release
How can Somatostatin decrease acid release?
Somatostatin released from D cells can act on the SSTR2’s on Parietal cells which inhibit H+ release
How can Histamine cause acid release?
Histamine acts on the HRH2’s on parietal cells, causing H+ release (also act on the HRH2’s on D cells, causing Somatostatin release)
What are the effects of Octreotide on plasma levels of growth hormone in acromegaly?
By 108 weeks of treatment, the amount of growth hormone is normalized
How are GI Peptides and Body Weight Control related?
Obesity is associated with the metabolic syndrome, chronic diseases like DM, HTN, and heart disease. Highly resistant to treatment with most of the weight lost regained within 5 years after dieting. Binge eating is implicated for more than 25% of the over weight population and is related to dysfunction of GI peptide signaling
What are the Incretins?
A group of GI hormones (GLP-1, GIP) that lower blood glucose by: increasing insulin release and inhibiting glucagon release after eating, slowing the rate of nutrient absorption and reducing food intake by reducing gastric emptying
What is the GI peptide control of food intake (GLP-1)?
Released in the lower gut. Decreases food intake by slowing gastric emptying; reduced hunger and increased fullness ratings
How is GLP-1 degraded?
Rapidly by dipeptidyl peptidase 4 (DPP-4). Half-life of 1-2 minutes
What are some synthetic analogues of GLP-1?
Extenatide (Byetta): injectable, with a half life of 2.4 hours; multiple injections required. Liraglutide (Victoza): injectable, with a half-life of 11-15 hours; once a day injection
What are some Dipeptidyl Peptidase-4 (DPP-4) Inhibitors?
Sitagliptin (Januvia): effective in improving blood glucose control when used alone or with other diabetes meds. Saxagliptin (Onglyza): used alone or in combination with other oral diabetes medicines; may worsen peripheral edema when used with TDZ
What is the GI peptide control of food intake (Ghrelin)?
Produced mainly by the stomach. Increased food intake when administered to humans. Level rises before meals and falls following meals. The higher the energy value of a meal the larger the postprandial decline. Level increases from the morning to the evening, reaches higher peak before dinner than before breakfast. Level rises following weight loss in obese subjects. Insulin and somatostatin strongly inhibit Ghrelin expression and secretion
What is the GI peptide control of food intake (Cholecystokinin (CCK))?
After a meal, CCK is released from endocrine 1 cells of the duodenum and the jejunum. Reduces the sensation of hunger in part by inhibiting gastric emptying. Administration to humans inhibits food intake. A decrease in plasma CCK correlates with a decreased fullness and increased hunger
What is the GI peptide control of food intake (Peptide YY (3-36))?
Secreted from specialized endocrine L cells of the large bowel. Circulating levels suppressed during fasting. Released into circulation within 15 minutes after meals and peaks in about 1 hour. Infusion of PYY in normal weight humans reduced 24-hour food intake. PYY levels in obese humans are reduced but anorectic effect is preserved
What is known as the “hunger hormone”?
Ghrelin. When this hormone level is high it indicates the need to eat. Causes an increase in food intake
