GIT Hormones and Digestion

### GIT Hormones

• Autocrine communication is within a single cell.
• Paracrine communication is between neighbouring cells.
• Endocrine communication is between distant cells via hormones in the bloodstream.
• The term hormone can refer to all three types of signaling.

### Types of GIT hormones

• There are many GI peptides/amines with various functions.
• Only five are considered to be true hormones (enter circulation): gastrin, cholecystokinin (CCK), secretin, glucose-dependent insulinotropic peptide (GIP), and motilin.
• Some peptides are endocrine, some paracrine, and some neural.
• These peptides are released from enteroendocrine cells distributed throughout the mucosa, not organized in glands.
• The duodenum and jejunum are the primary sites for hormone release.

Gastric Phases of Digestion

• Cephalic Phase: Begins with sight, smell, or thought of food. Triggers gastrin release and secretion of mucus, HCl, and pepsinogen.
• Gastric Phase: Stomach stretching activates stretch receptors, stimulating peristalsis (mixing) and gastric emptying
• Intestinal Phase: Begins with activation of receptors in the small intestine. Inhibition of gastric secretion by CCK and secretin slows gastric emptying.

### Gastrin and CCK

• Gastrin and CCK are structurally related peptides that act on CCK receptors.
• Both have a shared C-terminal sequence (Gly-Trp-Met-Asp-Phe), essential for activity.
• Gastrin (17 amino acids) and CCK (33 amino acids) can both act on each other's receptors.
• CCK-1 receptors are primarily found in the gallbladder (CCK).
• CCK-2 (or gastrin) receptors are primarily found in the stomach (gastrin).

### Gastrin Release

• G cells in the antrum of the stomach contain the highest concentration of gastrin.
• G cells are also found in the duodenum.
• Stimuli for Gastrin Release:
  • Cephalic Phase: Gastrin-releasing peptide (GRP) is the neurotransmitter released via vagovagal stimulation.
  • Gastric Phase: Stomach stretching stimulates GRP release.
  • Gastric and Intestinal Phase: Breakdown of proteins to amino acids also stimulates gastrin release.
• Gastrin Actions:
  • Increases acid secretion from oxyntic/parietal cells via CCK-2 receptors.
  • Stimulates histamine release from ECL cells, leading to further acid secretion.
  • Acts as a trophic agent, promoting growth of stomach mucosa.
  • Stimulates splanchnic blood flow.

### Cholecystokinin (CCK) Release

• I cells located in the upper small intestine (duodenum and jejunum) release CCK.
• CCK release is stimulated by proteins and fats (peptides, single amino acids, fatty acids, monoglycerides).
• Sensory afferents (nerve fibers) are activated, and I cells may directly sense substrates during absorption.

### Cholecystokinin (CCK) Actions

• Most actions are on the gallbladder and pancreas.
• Effects on Gastric Acid Secretion:
  • Stimulates acid secretion via CCK-2 receptors.
  • Inhibits acid secretion via CCK-1 receptors, stimulating somatostatin release from D cells.
• Increases splanchnic blood flow.

### Secretin

• Secretin shares amino acid residues with GIP, VIP, and glucagon.
• S cells in the duodenum release secretin.
• Stimuli for Secretin Release:
  • Low pH and, to a lesser extent, fatty acids.
  • Secretin-releasing peptide activates sensory afferent fibers.
  • S cells may directly sense pH and fatty acids.
• Secretin Actions:
  • Stimulates pancreatic secretions (aqueous solution, bicarbonate).
  • Stimulates insulin release.
  • Decreases gastric acid secretion and gastric motility (via somatostatin and vagal pathways).
  • Increases splanchnic blood flow.

### Other Hormones

• Somatostatin is released from delta (D) cells in the pancreas and stomach.

  • Stimulated by CCK and ACh (released in response to increased blood glucose and amino acids).
  • Acts as an inhibitor, decreasing motility, acid secretion, and blood flow.

• Motilin is released from enteroendocrine (“Mo”) cells in the mucosa of the upper GI tract.

  • Released in 90-minute cycles, and inhibited by food intake.
  • Responsible for the migrating motor complex, which assists in clearing foreign bodies.

• Gastric Inhibitory Peptide (GIP), now called glucose-dependent insulinotropic polypeptide (GIP), is released from K cells in the duodenum and jejunum.

  • Stimulated by the presence of food in the upper small intestine.
  • Inhibits gastric secretions and motility.
  • Primarily stimulates insulin secretion.

• Serotonin (5-HT) is released from enterochromaffin cells.

  • Involved in vomiting.
  • Some anti-emetics (e.g., ondansetron) block 5-HT3 receptors on sensory afferent fibers.

Pancreatic Secretion

• Gastric Phase: Stomach distension activates vagovagal reflexes, stimulating pancreatic secretion. Gastrin plays a minimal role.
• Intestinal Phase: The presence of digestion products (70-80% of stimulation) and H+ in the small intestine stimulates pancreatic secretion.
  • Secretin released by acid stimulates ductal cells, increasing aqueous volume and pH (due to HCO3-).
  • CCK released by fat and protein digestion stimulates acinar cells to increase enzyme secretion.
  • CCK acts indirectly via vagal afferent fibers.

### Bile Secretion

• Bile is produced by hepatocytes (liver cells), stored in the gallbladder, and released into the duodenum.
  • Bile is crucial for fat digestion and consists of: water, bilirubin, cholesterol, bile salts, and other fats.
  • Secretin stimulates water and bicarbonate secretion from bile ducts.
  • CCK acts on CCK-1 receptors in the gallbladder to contract it and relax the sphincter of Oddi, releasing bile acids into the small intestine.

### Central Control of Food Intake

• The hypothalamus plays a crucial role in regulating food intake.
• Neuropeptide Y (NPY) and proopiomelanocortin (POMC) systems:
  • NPY system: stimulates food intake.
  • POMC system: inhibits food intake.
  • These systems have antagonistic effects.
  • CCK inhibits food intake by activating POMC neurons.
• CCK also acts on the vagus nerve, contributing to satiety.

Neurohumoral Signals

• The cephalic phase of gastric secretion is initiated by sight, smell or thoughts of food, releasing gastrin into the blood and stimulating secretion of mucus, HCl and pepsinogen.
• During the gastric phase, stretching of the stomach activates stretch receptors, stimulating peristalsis (mixing) and gastric emptying.
• The intestinal phase begins with activation of receptors in the small intestines, inhibiting gastric secretion by CCK and secretin, and slowing gastric emptying.

Gastrin and Cholecystokinin (CCK)

• Gastrin and CCK are structurally related peptide hormones that act at the CCK receptors.
• They share the C-terminal sequence, essential for activity: Gly – Trp – Met – Asp – Phe.
• CCK-1 receptor is found in the gallbladder, predominantly activated by CCK.
• CCK-2 (or gastrin) receptor is found in the stomach, predominantly activated by gastrin.

Gastrin Release

• Gastrin-containing cells (G cells) are densest in the antrum of the stomach, with some in the duodenum.
• Gastrin release is triggered by different stimuli across each gastric phase:
  • Cephalic and gastric phases: vagovagal stimulation, gastrin releasing hormone (GRP) as neurotransmitter.
  • Gastric and intestinal phases: breakdown of protein to amino acids also stimulates gastrin release.

Pancreatic Secretions

• The pancreas has both endocrine and exocrine secretions.
• Endocrine secretions (glucagon and insulin) are not the focus here.
• Exocrine secretions consist of:
  • An aqueous component (mainly Na+ and HCO3- secreted by ductal epithelial cells).
  • A proteinaceous/enzymatic component (inactive precursors of digestive enzymes secreted by acinar cells).

Control of Pancreatic Secretion

• The pancreas produces a basal secretion of enzymes and fluid during the interdigestive period, coordinated by the parasympathetic nervous system, aided by CCK.
• Pancreatic juice secretion increases up to 20 times during a meal, driven by stimulatory and inhibitory mechanisms across cephalic, gastric, and intestinal phases.

Cephalic Phase of Pancreatic Secretion

• Stimuli: conditioned reflexes, smell, taste, chewing, and swallowing.
• Afferent impulses travel to the vagal nucleus.
• Vagal ACh stimulates both acinar and ductal secretions.
• Gastrin (released by the vagus) stimulates acinar cells, the role in humans is unclear.

Gastric Phase of Pancreatic Secretion

• Stimulation is mediated by the same mechanisms as the cephalic phase.
• Distension of the stomach wall initiates vagovagal reflexes to the pancreas.
• Gastrin plays little to no role in stimulating the pancreas.

Intestinal Phase of Pancreatic Secretion

• Presence of digestion products and H+ in the small intestine accounts for 70-80% of pancreatic secretion stimulation.
• Secretin and CCK account for almost all hormonal stimulation:
  • Secretin release, stimulated by acid and long chain fatty acids, stimulates the ductal cells to increase the aqueous solution, increasing volume and pH.
  • CCK, stimulated by fat and protein digestion, stimulates the acinar cells to increase enzyme secretion.

Bile

• Secreted by liver cells (hepatocytes), stored in the gall bladder, and released into the duodenum.
• Crucial for fat digestion, consisting of water, bilirubin, cholesterol, bile salts, and other fats.
• Secretin stimulates water and bicarbonate secretion from bile ducts.
• CCK constricts the gall bladder and relaxes the sphincter of Oddi, releasing bile acids.

Food Intake - Peripheral Regulation

• The vagus nerve carries afferent fibers relaying information to the nucleus tractus solitarius in the brain.
• Input can also cause efferent signals by vagal nerves, resulting in changes in gut function: "vagovagal reflex."
• Vagal stimulation induces satiety and inhibits feeding.
• Blocking of vagal afferents eliminates satiety.
• Insulin, released from pancreatic β-cells after a meal, acts directly on the hypothalamus to induce satiety.
• Leptin, released from adipocytes, stimulates the POMC pathway, inhibits the NPY pathway, inducing satiety.

Food Intake - Gastric (Inhibitors)

• Local gastric stimuli pass information back to the hypothalamus.
• Distension of the stomach stimulates vagal afferents and inhibits feeding.
• CCK, released due to food presence in the small intestine, stimulates satiety and inhibits feeding, by stimulating vagal afferents and insulin release.
• Peptide YY, released by enteroendocrine cells of the ileum and colon by fat digestion products, stimulates satiety, directly inhibiting NPY orexigenic nerves.

Food Intake - Stimulants

• Ghrelin is released from oxyntic glands in the stomach, also released from extra-gastric sites.
• Stimulates release of growth hormone and directly stimulates orexigenic NPY neurons (increased food intake).
• Ghrelin release is not affected by protein intake or distention.
• Dopaminergic neurons from the ventral tegmental area (VTA) of the midbrain (reward pathways) influence the hypothalamus, affected by ghrelin, leptin etc.

Summary

• Gastrin: stimulated by acid, protein, distension, nervous input.
• CCK: stimulated by fats, carbohydrates, distension, nervous input.
• Secretin: stimulated by acid, carbohydrates, distension, nervous input.
• GIP: stimulated by carbohydrates, distension, nervous input.
• Motilin: stimulated by fats, carbohydrates, distension, nervous input.

Summary

• Gastrin: decreases gastric emptying, increases gastric motility, increases acid secretion.
• CCK: decreases gastric emptying, increases pancreatic secretion, increases gallbladder contraction.
• Secretin: increases pancreatic secretion, increases bicarbonate secretion, increases bile duct secretion.
• GIP: increases insulin release.
• Motilin: increases intestinal motility.

GI Hormone Criteria

• Step 1: Does a meal or other physiological event provide a stimulus for one part of the GI tract to affect another?
• Step 2: Does this affect persist after nervous communication between those parts is removed?
• Step 3: Can you isolate a substance from the site of the stimulus that when injected mimics the effect of the stimulus?
• Step 4: Can you identify the substance chemically and synthesise it?

Explore the intricate roles of GIT hormones in digestion with this quiz. Learn about the different types of communication within the body, the distinction between true hormones, and their functions. This quiz covers the gastric phases of digestion, focusing on key peptides and their actions.