Enteroendocrine cells are specialized hormone-secreting epithelial cells located in the lining of the gastrointestinal (GI) tract and pancreas. These cells function as key regulators of digestion, metabolism, and gut-brain signaling by releasing hormones and signaling molecules in response to stimuli such as nutrients, mechanical stress, or neural signals. Enteroendocrine cells are part of the diffuse neuroendocrine system and are often referred to as the “endocrine cells of the gut.” They secrete a variety of hormones, including gastrin, secretin, cholecystokinin (CCK), and serotonin, which help coordinate digestive processes and maintain homeostasis.
Structure
Enteroendocrine cells have a distinct structure tailored to their hormone-secreting function. These cells are scattered among the epithelial lining of the gastrointestinal (GI) tract and are characterized by specific structural features:
Shape and Orientation
- Polarized Cells: Enteroendocrine cells are polarized, meaning they have distinct apical and basal regions.
- Apical Region: The apical side may have microvilli to sense luminal contents, such as nutrients or chemicals in the GI tract.
- Basal Region: The basal portion contains secretory granules loaded with hormones or signaling molecules, which are released into the bloodstream or local tissue upon stimulation.
Secretory Granules
- These granules store hormones and are located in the basal cytoplasm of the cell.
- Granules are released by exocytosis in response to specific stimuli, ensuring rapid hormone secretion when needed.
Cytoplasmic Organelles
- Endoplasmic Reticulum (ER): Well-developed rough ER for the synthesis of peptide hormones.
- Golgi Apparatus: Prominent for the packaging and processing of hormones into secretory granules.
- Mitochondria: Abundant to meet the high energy demands of hormone synthesis and secretion.
Receptors and Sensors
Enteroendocrine cells express specific receptors on their apical membrane that detect luminal stimuli, such as nutrients (amino acids, glucose, lipids), pH changes, or mechanical stretch.
Cellular Distribution
They are scattered as individual cells within the epithelial lining of the GI tract and are not organized into clusters like traditional endocrine glands.
Location
Enteroendocrine cells are distributed throughout the epithelial lining of the gastrointestinal (GI) tract and other associated organs. Their location is tailored to the specific digestive or regulatory functions of the hormones they produce.
Below are the primary sites where enteroendocrine cells are found:
Gastrointestinal Tract
- Stomach:
- Found in the gastric glands, especially in the antrum.
- Examples: G-cells secrete gastrin, and D-cells secrete somatostatin.
- Small Intestine:
- Large Intestine:
- Present in the colonic epithelium.
- Example: Enterochromaffin cells secrete serotonin, which regulates gut motility.
Pancreas
Enteroendocrine cells are also present in the islets of Langerhans, where they secrete hormones such as insulin, glucagon, and somatostatin to regulate blood glucose levels.
Other Locations
- Appendix: Enteroendocrine cells contribute to local immune responses and gut-brain communication.
- Rectum: These cells secrete regulatory hormones that influence motility and defecation reflexes.
Types of Enteroendocrine Cells
Enteroendocrine cells are classified based on the hormones they produce and their location within the gastrointestinal (GI) tract.
Below are the major types of enteroendocrine cells and their key characteristics:
G-Cells
- Location: Found predominantly in the antrum of the stomach.
- Hormone Secreted: Gastrin.
- Function: Stimulates gastric acid (HCl) secretion by parietal cells and promotes gastric motility.
D-Cells
- Location: Present in the stomach, pancreas, and small intestine.
- Hormone Secreted: Somatostatin.[7]
- Function: Inhibits the release of other hormones like gastrin, insulin, and glucagon, helping to regulate digestive processes.
I-Cells
- Location: Found in the duodenum and jejunum.
- Hormone Secreted: Cholecystokinin (CCK).
- Function: Stimulates the release of bile from the gallbladder and pancreatic enzymes, aiding in fat and protein digestion.
S-Cells
- Location: Primarily in the duodenum.
- Hormone Secreted: Secretin.
- Function: Stimulates the pancreas to secrete bicarbonate, neutralizing stomach acid in the small intestine.
Enterochromaffin (EC) Cells
- Location: Throughout the GI tract, especially in the small intestine and colon.
- Hormone Secreted: Serotonin.
- Function: Regulates gut motility and initiates peristaltic reflexes.
K-Cells
- Location: Found in the duodenum and jejunum.
- Hormone Secreted: Gastric inhibitory peptide (GIP).
- Function: Inhibits gastric acid secretion and enhances insulin release in response to glucose.
L-Cells
- Location: Present in the ileum and colon.
- Hormone Secreted: Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
- Function: Regulates appetite, slows gastric emptying, and stimulates insulin release.
N-Cells
- Location: Found in the small intestine.
- Hormone Secreted: Neurotensin.
- Function: Influences intestinal motility and blood flow.
Enterochromaffin-like (ECL) Cells
- Location: Gastric glands in the stomach.
- Hormone Secreted: Histamine.
- Function: Stimulates parietal cells to secrete gastric acid.
Hormones Secreted by Enteroendocrine Cells
Enteroendocrine cells produce a wide range of hormones and signaling molecules that regulate various digestive and metabolic processes. Below is a detailed list of the major hormones secreted by these cells, along with their sources and roles:
Gastrin
- Source: G-cells in the stomach’s antrum.
- Function: Stimulates parietal cells to produce hydrochloric acid (HCl) and promotes gastric motility.
Cholecystokinin (CCK)
- Source: I-cells in the duodenum and jejunum.[5]
- Function: Stimulates the release of bile from the gallbladder and pancreatic enzymes for fat and protein digestion. It also slows gastric emptying.
Secretin
- Source: S-cells in the duodenum.
- Function: Stimulates the pancreas to release bicarbonate-rich secretions to neutralize stomach acid in the small intestine.
Serotonin
- Source: Enterochromaffin (EC) cells throughout the GI tract.
- Function: Regulates gut motility, initiates peristalsis, and plays a role in nausea and vomiting reflexes.
Somatostatin
- Source: D-cells in the stomach, pancreas, and small intestine.
- Function: Inhibits the secretion of gastrin, insulin, glucagon, and other hormones, maintaining balance in digestive processes.
Gastric Inhibitory Peptide (GIP)
- Source: K-cells in the duodenum and jejunum.
- Function: Reduces gastric acid secretion and enhances insulin secretion in response to glucose.
Glucagon-Like Peptide-1 (GLP-1)
- Source: L-cells in the ileum and colon.
- Function: Stimulates insulin secretion, slows gastric emptying, and regulates appetite by increasing feelings of satiety.[3]
Peptide YY (PYY)
- Source: L-cells in the ileum and colon.
- Function: Reduces appetite and slows intestinal transit to enhance nutrient absorption.
Histamine
- Source: Enterochromaffin-like (ECL) cells in the stomach.
- Function: Stimulates gastric acid secretion by acting on parietal cells.
Neurotensin
- Source: N-cells in the small intestine.
- Function: Modulates intestinal motility and blood flow, as well as stimulating pancreatic secretion.[1]
Motilin
- Source: M-cells in the duodenum and jejunum.
- Function: Regulates migrating motor complexes (MMC) to promote gastric and intestinal motility during fasting.
These hormones, secreted in response to food intake, pH changes, and mechanical stimuli, orchestrate the complex processes of digestion, nutrient absorption, and metabolic regulation.
Function
Enteroendocrine cells play a vital role in the regulation of digestive processes, nutrient absorption, and systemic metabolic functions.[8] Their functions are diverse and highly specialized, depending on the hormones they secrete and their location within the gastrointestinal (GI) tract. Below are their key functions:
Regulation of Gastric Activity
- Acid Secretion: Enteroendocrine cells like G-cells secrete gastrin, which stimulates parietal cells to produce hydrochloric acid, essential for protein digestion.
- Inhibition of Gastric Activity: D-cells release somatostatin, which inhibits excessive acid secretion and prevents overactivation of gastric processes.
Coordination of Digestive Enzyme and Bile Release
Cholecystokinin (CCK): Secreted by I-cells in response to fats and proteins in the duodenum, CCK stimulates:
- The pancreas to release digestive enzymes.
- The gallbladder to release bile, aiding fat emulsification and digestion.
Neutralization of Stomach Acid
Secretin: Produced by S-cells in the duodenum when acidic chyme enters the small intestine, secretin stimulates the pancreas to release bicarbonate-rich secretions.[6] This neutralizes stomach acid and provides an optimal environment for enzymatic digestion in the small intestine.
Regulation of Gut Motility
- Serotonin (5-HT): Secreted by enterochromaffin cells, serotonin coordinates intestinal peristalsis and motility, ensuring proper movement of food through the GI tract.
- Motilin: Stimulates migrating motor complexes (MMC), promoting gastric and intestinal motility during fasting periods.
Blood Glucose Regulation
- Glucagon-Like Peptide-1 (GLP-1):
- Enhances insulin secretion from pancreatic beta cells in response to elevated blood glucose levels.
- Inhibits glucagon release, reducing hepatic glucose production.
- Gastric Inhibitory Peptide (GIP): Stimulates insulin secretion during the absorptive phase of digestion.
Appetite Regulation
- Peptide YY (PYY):
- Reduces appetite and slows intestinal transit after meals, allowing more efficient nutrient absorption.
- GLP-1: Increases satiety, helping regulate food intake.
Immune and Barrier Function
Enteroendocrine cells also play a role in maintaining the integrity of the gut barrier and modulating immune responses. For example, their secretions can influence gut-associated lymphoid tissue (GALT) activity, which protects against pathogens.
Gut-Brain Communication
Enteroendocrine cells act as sensors, transmitting information about the luminal contents to the central nervous system (CNS) via hormones like serotonin and GLP-1. This gut-brain signaling regulates hunger, satiety, and digestive reflexes.
Clinical Significance
Enteroendocrine cells are crucial regulators of gastrointestinal and metabolic functions, and their dysfunction is associated with several clinical conditions. Overproduction of hormones, such as gastrin in Zollinger-Ellison syndrome, can lead to peptic ulcers, while impaired secretion of GLP-1 and GIP contributes to type 2 diabetes and poor glucose regulation. These cells are also implicated in irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) due to altered serotonin and peptide secretion, which affect motility and inflammation.[4]
Additionally, enteroendocrine cells are the origin of neuroendocrine tumors like carcinoid tumors and gastrinomas, which cause excessive hormone production, leading to systemic symptoms such as diarrhea and flushing.[2] Their role in gut-brain communication links them to conditions like obesity and mood disorders. Enteroendocrine-targeted therapies, including GLP-1 analogs and somatostatin analogs, have become important in managing diabetes, obesity, and neuroendocrine tumors.
