Gastrointestinal Peptides
A survey of the major GI hormones — gastrin, CCK, secretin, GIP, and GLP-1 — their sources, functions, and clinical significance.
Overview
The gastrointestinal tract is the largest endocrine organ in the body. Enteroendocrine cells scattered throughout the gut epithelium secrete peptide hormones in response to nutrients, pH changes, and neural signals. These hormones coordinate digestion, absorption, and metabolic homeostasis.
Major GI Peptides
Gastrin
- Source: G cells in the gastric antrum
- Stimulus: Peptides and amino acids in the stomach, vagal stimulation
- Function: Stimulates gastric acid secretion from parietal cells; promotes gastric mucosal growth
- Active form: G-17 (17 amino acids)
Cholecystokinin (CCK)
- Source: I cells in the duodenum and jejunum
- Stimulus: Fatty acids and amino acids in the duodenum
- Function: Stimulates gallbladder contraction and pancreatic enzyme secretion; promotes satiety
- Active forms: CCK-8, CCK-33, CCK-58
Secretin
- Source: S cells in the duodenum
- Stimulus: Acidic chyme entering the duodenum
- Function: Stimulates bicarbonate secretion from the pancreas; inhibits gastric acid secretion
- Note: The first hormone ever discovered (1902)
Glucose-dependent Insulinotropic Peptide (GIP)
- Source: K cells in the duodenum and jejunum
- Stimulus: Glucose and fat in the duodenum
- Function: Potentiates insulin secretion (incretin effect); stimulates lipogenesis
Glucagon-like Peptide-1 (GLP-1)
- Source: L cells in the ileum and colon
- Stimulus: Nutrients reaching the distal gut
- Function: Potentiates insulin secretion; inhibits glucagon secretion; slows gastric emptying; promotes satiety
Enteroendocrine Cell Signaling
Enteroendocrine cells are polarized epithelial cells with microvilli facing the gut lumen. When nutrients bind receptors on the apical surface, the cell releases hormones from the basolateral side into the bloodstream. Some hormones also activate vagal afferent nerves, contributing to the gut-brain axis.
The Incretin Effect
Oral glucose produces a significantly greater insulin response than intravenous glucose at the same blood glucose level. This is the incretin effect, driven primarily by GLP-1 and GIP. In type 2 diabetes, the incretin effect is diminished, largely due to reduced GLP-1 secretion or action.
Summary Table
| Peptide | Source Cell | Primary Stimulus | Key Function |
|---|---|---|---|
| Gastrin | G cells (antrum) | Peptides/amino acids | Gastric acid secretion |
| CCK | I cells (duodenum) | Fatty acids, amino acids | Gallbladder contraction, pancreatic enzymes |
| Secretin | S cells (duodenum) | Acidic chyme | Bicarbonate secretion |
| GIP | K cells (duodenum) | Glucose, fat | Insulin potentiation |
| GLP-1 | L cells (ileum/colon) | Distal nutrients | Insulin potentiation, satiety |
Clinical Relevance
GLP-1 receptor agonists (e.g., semaglutide, liraglutide) are now first-line therapies for type 2 diabetes and obesity. They exploit the incretin pathway to enhance insulin secretion and promote weight loss.