GI Hormones

The GI tract is the largest endocrine organ in the body. Specialized cells scattered throughout the stomach and small intestine release hormones that coordinate digestion like a relay team - each hormone passes the baton to trigger the next step. These hormones use the same signaling mechanisms as other endocrine hormones. The MCAT expects you to know the four major GI hormones, their triggers, and their effects.

The Big Four GI Hormones

Gastrin

• Source: G cells in the stomach antrum (pyloric region)
• Trigger: Stomach distension, peptides/amino acids in the stomach, vagal stimulation (parasympathetic)
• Effects:
  • Stimulates parietal cells to secrete HCl
  • Stimulates chief cells to secrete pepsinogen
  • Stimulates gastric motility
  • Promotes growth of gastric mucosa (trophic effect)
• Inhibited by: Low stomach pH (<2), somatostatin, secretin

Gastrin operates in a negative feedback loop: it stimulates HCl production, and when the stomach becomes sufficiently acidic (pH <2), gastrin release is suppressed.

Secretin

• Source: S cells in the duodenal mucosa
• Trigger: Acidic chyme entering the duodenum (pH <4.5)
• Effects:
  • Stimulates pancreatic duct cells to release bicarbonate (neutralizes acid)
  • Stimulates bile secretion from the liver
  • Inhibits gastrin release and gastric acid secretion (slows stomach activity)
• Inhibited by: Rising duodenal pH (the acid has been neutralized - job done)

Cholecystokinin (CCK)

• Source: I cells in the duodenal and jejunal mucosa
• Trigger: Fatty acids and amino acids in the duodenum
• Effects:
  • Stimulates gallbladder contraction (releases bile)
  • Stimulates pancreatic acinar cells to release digestive enzymes
  • Slows gastric emptying (gives the duodenum time to process)
  • Stimulates satiety (reduces appetite via hypothalamus)
  • Relaxes the sphincter of Oddi
• Inhibited by: Completion of fat and protein digestion

CCK is the reason fatty meals make you feel full faster and stay in your stomach longer.

Gastric Inhibitory Peptide (GIP)

Also called glucose-dependent insulinotropic peptide (same abbreviation - GIP).

• Source: K cells in the duodenum and jejunum
• Trigger: Glucose, fatty acids, and amino acids in the duodenum
• Effects:
  • Stimulates insulin release from pancreatic beta cells (the “incretin” effect)
  • Inhibits gastric acid secretion and motility (slows stomach)
  • Slows gastric emptying
• Key concept: Oral glucose causes more insulin release than the same dose of IV glucose, because GIP from the gut amplifies the pancreatic response (the “incretin effect”)

Master GI Hormone Table

Hunger and Satiety Hormones

Two hormones regulate appetite at the level of the hypothalamus:

Ghrelin - “the hunger hormone”

• Source: specialized cells in the stomach fundus
• Rises sharply before meals (when stomach is empty)
• Falls after eating
• Stimulates appetite, food-seeking behavior, gastric motility, gastric acid secretion, and growth hormone release
• Short-term regulator (meal-to-meal)

Leptin - “the satiety hormone”

• Source: adipose tissue (fat cells)
• Higher body fat = higher leptin levels
• Signals the hypothalamus that energy stores are sufficient
• Reduces appetite, increases energy expenditure
• Long-term regulator (body weight over weeks/months)
• Does NOT act directly on the stomach or intestines