Gastrointestinal Hormones PDF

Gastrointestinal Hormones 24/10/31 A.F.Abdel-Aziz 1 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrointestinal Hormones 24/10/31...

Gastrointestinal Hormones 24/10/31 A.F.Abdel-Aziz 1 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrointestinal Hormones 24/10/31 A.F.Abdel-Aziz 2 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrointestinal Hormones The GI tract is both a major endocrine organ and a major target for many hormones, released locally and from other sites. GI hormones are present in the Gut and in the Central Nervous System (CNS) GI hormones can influence in: Motility, Secretion, Digestion and Absorption of the Gut. Regulate of Bile flow and secretion of pancreatic hormones. Can affect on tonicity of the vascular walls, blood pressure and cardiac output. They have a role as Neurotransmitter when they are released from Nerve synapses. 24/10/31 A.F.Abdel-Aziz 3 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrointestinal Hormones Glucagon-like peptide-1 (GLP-1) Glucagon-like peptide-2 (GLP-2) Glucose-dependent insulinotropic polypeptide (GIP) Glicentin Oxyntomodulin Gastrin Cholecystokinin (CCK) Secretin 24/10/31 A.F.Abdel-Aziz 4 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrointestinal Hormones Vasoactive intestinal peptide (VIP) Pancreatic polypeptide (PP) Enkephalins Neurotensin Motilin 24/10/31 A.F.Abdel-Aziz 5 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  More endocrine fun to come! 24/10/31 A.F.Abdel-Aziz 6 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gut hormones The first TWO Gut hormones constitute the class of molecules referred to as the incretins: Incretins are molecules associated with food intake-stimulation of insulin secretion from the pancreas: 1- Glucagon-like peptides-1(GLP-1) and 2- Glucose-dependent insulinotropic peptide (GIP). 24/10/31 A.F.Abdel-Aziz 7 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Glucagon-like peptide-1(GLP-1) GLP-1 is derived from the product of the proglucagon gene. GLP-1 is secreted from intestinal enteroendocrine L-cells that are found predominantly in the ileum and colon with some production from these cell types in the duodenum and jejunum 24/10/31 A.F.Abdel-Aziz 8 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Structure of preproglucagon product GRPP = glicentin-related pancreatic peptide. IP = intervening peptide. GLP-2= glucagon-like peptide-2. 24/10/31 A.F.Abdel-Aziz 9 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Secreted of Glucagon-like peptide-1 (GLP-1) Upon nutrient ingestion GLP-1 is secreted from intestinal enteroendocrine L-cells that are found in : ileum and colon duodenum and jejunum. 24/10/31 A.F.Abdel-Aziz 10 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  physiological responses to GLP-1 This activity has significance in the context of diabetes The action of GLP-1 at the level of insulin and glucagon secretion results in significant reduction in circulating levels of glucose following nutrient intake. Then glucose lowering activity of GLP-1 is highly transient as the half-life of this hormone in the circulation is less than 2 minutes. 24/10/31 A.F.Abdel-Aziz 11 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  The primary Function of GLP-1 Reduction in circulating levels of glucose following nutrient intake. Inhibition of glucagon secretion and Inhibition of gastric acid secretion and gastric emptying. 24/10/31 A.F.Abdel-Aziz 12 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Glucagon-like peptide-1 (GLP-1) *The glucose lowering activity of GLP-1 *Removal of bioactive GLP-1 is a consequence of N-terminal proteolysis catalyzed by dipeptidyl peptidase IV (DPP IV). DPP IV is also known as the lymphocyte surface antigen CD26 24/10/31 A.F.Abdel-Aziz 13 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  GLP-1 receptor o The GLP-1R is a typical seven-transmembrane spanning receptor coupled to G-protein activation, increased cAMP production and activation of PKA. o Other major responses to the actions of GLP-1 include pancreatic B-cell proliferation and expansion concommitant with a reduction of B-cell apoptosis (death). o In addition, GLP-1 activity results in increased expression of the glucose transporter-2 (GLUT-2) and glucokinase genes in pancreatic cells. 24/10/31 A.F.Abdel-Aziz 14 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Glucose-dependent insulinotropic peptide (GIP) o GIP is consists of 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. o GIP is synthesized by enteroendocrine K-cells whose locations are primarily in the duodenum and proximal jejunum. o GIP was inhibition by gastric acid secretion and was thus, originally called gastric inhibitory peptide. 24/10/31 A.F.Abdel-Aziz 15 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 7-2-3: ANATOMY SUMMARY: Hormones  Functions of GIP on fat metabolism oThis gut hormone possessed potent stimulation of glucose-dependent insulin secretion. Effects of GIP on fat metabolism , Stimulate the lipoprotein lipase activity leading to increased uptake and incorporation of fatty acids by adipocytes GIP has a positive effects on pancreatic B-cell proliferation and survival similar to GLP-1 GIP does not affect glucagon secretion nor gastric emptying Like GLP-1, GIP is inactivated through the action of dipeptidyl peptidase IV (DPP IV) 24/10/31 A.F.Abdel-Aziz 16 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastrin Gastrin is sereted from G-cells of the Stomach Gastrin is a linear peptide and synthesized as a preprohormone Circulating Gastrin is gastrin-34 (big gastrin), but full biologic activity is present in the smallest peptide (gastrin-14 or mini gastrin). Full bioactivity is the five C-terminal amino acids of gastrin, which is known as pentagastrin. The five C-terminal amino acids of gastrin and cholecystokinin are identical, which explains their overlapping biological effects. 24/10/31 A.F.Abdel-Aziz 17 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Structure of Gastrin 24/10/31 A.F.Abdel-Aziz 18 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Function of Gastrin Stimulate secretion of gastric Pepsinogen. Stimulate secretion of pancreatic biocarbonate and enzymes. Increased gastric and intestinal motility. Increased blood flow to the stomach 24/10/31 A.F.Abdel-Aziz 19 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Stimulation and Inhibition of Gastrin Gastrin is stimulated by : Amino acid and proteins Alcohol, Caffeine and Insuline Intravenous Ca++ Smelling, Tasting, Chewing and swalling of food. Gastrin secretion is inhibited by Gastric acid Clinical significance of Gastrin: Gastrin helpful in the diagnosis of Zollinger-Ellison syndrome (duodenal, pancreatic and gastric cancer ) 24/10/31 A.F.Abdel-Aziz 20 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Cholecystokinin (CCK) Function of Cholecystokinin (CCK) : Activate gallbladder contraction Stimulate secretion of pancreatic enzymes Increased motility of duodenum and intestine 24/10/31 A.F.Abdel-Aziz 21 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Cholecystokinin (CCK) CCK is stimulate by : Amino acid and proteins and fatty acids Gastric HCl CCK is inhibited by : Somatostatin hormone Clinical Significance of CCK : Increased CCK in : 1-Fatty acid intolerance 2- Postgastrectomy 3-Irritable bowel syndrome. 4- Gastric ulcer 24/10/31 A.F.Abdel-Aziz 22 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Secretin Function of Secretin : Stimulate secretion of pancreatic bicarbonates and enzymes Stimulates secretion of water from the liver. Increased hepatic flow. Weak stimulation of insulin secretion. Stimulate parathyroid hormone release. Reduction of gastric and duodenal motility. Inhibits of gastric release and therefore, inhibits Gastric acid secretion. 24/10/31 A.F.Abdel-Aziz 23 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Secretin Inhibition of secretin by Somatostsin hormone. Secretin is stmulates by: Alcohol and Food. Clinical Significance: Secretin in combination with CCK, may be useful for the detection of pancreatic diseases. 24/10/31 A.F.Abdel-Aziz 24 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Vasoactive Intestinal Polypeptide (VIP) Function of VIP: VIP act as neurotransmitter in the CNS. VIP causes vasodilation and relaxation of the smooth muscle of the genitourinary systems. VIP increase secretion of H2O and electrolyte from pancreas and gut. VIP stimulate release of some hormones from pancreas , gut and hypothalamus. VIP stimulate lipolysis, glycolysis and bile flow. VIP inhibit gastrin and gastric acid secretion. 24/10/31 A.F.Abdel-Aziz 25 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Vasoactive Intestinal Polypeptide (VIP) Inhibition of VIP by somatostatin hormone Clinical significance : VIP increased in : Verner-morrison syndrome (Pancreatic Cholera) Pancreatic tuomour Hepatic Cirrhosis Crohn's diseases 24/10/31 A.F.Abdel-Aziz 26 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Gastric Inhibitory Polypeptide (GIP) Function of GIP: Stimulate insulin secretion in hyperglycemia. Reduction of intestinal motility. Stimulate small intestine fluid and electrolytes. Inhibition of gastric acid, pepsin, and gastrin secretion. 24/10/31 A.F.Abdel-Aziz 27 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Clinical significance of GIP GIP is increased in : Starvation Prolonged fasting Type IV hyperlipoproteinemia Renal failure In some cases of diabetes In duodenal ulcer. Lowering GIP to baseline : Responses to glucose and TG. 24/10/31 A.F.Abdel-Aziz 28 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Ghrelin Ghrelin as the peptide hormone that potently stimulates release of growth hormone from the anterior pituitary. Ghrelin has a significant effects on appetite and energy balance. Source of Ghrelin is epithelial cells lining in the stomach. Smaller amounts are produced in the placenta, kidney, pituitary and hypothalamus (Ghrelin receptors are present on the cells in the pituitary that secrete growth hormone ) 24/10/31 A.F.Abdel-Aziz 29 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Control and Physiologic Effects of Ghrelin 1- Stimulation of growth hormone secretion: The Ghrelin signal is integrated with that of growth hormone releasing hormone and somatostatin to control the timing and magnitude of growth hormone secretion 2- Regulation of Energy Balance: In both rodents and humans, Ghrelin functions to increase hunger though its action on hypothalamic feeding centers. 24/10/31 A.F.Abdel-Aziz 30 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Control and Physiologic Effects of Ghrelin This makes sense relative to increasing plasma Ghrelin concentrations observed during fasting. Other effects of Ghrelin include stimulating gastric emptying and having a variety of positive effects on cardiovascular function (e.g. increased cardiac output). Overall, Ghrelin seems to be one of several hormonal signals that communicates the state of energy balance in the body to the brain 24/10/31 A.F.Abdel-Aziz 31 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Blood concentrations of Ghrelin are lowest shortly after consumption of a meal, then rise during the fast just prior to the next meal. The figure to the right shows this pattern based on assays of plasma Ghrelin in 10 humans during the course of a day 24/10/31 A.F.Abdel-Aziz 32 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Disease States of Ghrelin Ghrelin concentrations in blood are reduced in obese humans Patients with anorexia nervosa have higher than normal plasma Ghrelin levels, which decrease if weight gain occurs Prader-Willi syndrome is clearly a complex disease with many defects; it may be that excessive Ghrelin production contributes to the appetite and obesity components. 24/10/31 A.F.Abdel-Aziz 33 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings  Thanks for your attention 24/10/31 A.F.Abdel-Aziz 34 Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings