From the Guidelines
Secretin, CCK, enterokinase, and brush border enzymes all play crucial roles in macronutrient absorption through different mechanisms, with the most recent evidence from 2023 highlighting the importance of these hormones and enzymes in maintaining proper digestive function 1.
Mechanisms of Action
- Secretin primarily stimulates pancreatic bicarbonate secretion, which neutralizes stomach acid in the duodenum, creating an optimal pH environment for digestive enzymes to function, as noted in a study from 2002 1.
- Cholecystokinin (CCK) directly enhances fat absorption by stimulating gallbladder contraction to release bile salts that emulsify fats, while also triggering pancreatic enzyme secretion that breaks down proteins, fats, and carbohydrates.
- Enterokinase, produced by duodenal cells, specifically activates pancreatic trypsinogen into trypsin, initiating a cascade that activates other pancreatic proteases essential for protein digestion and absorption.
- Brush border enzymes, located on the microvilli of intestinal epithelial cells, are critical for the final stages of carbohydrate and protein digestion, converting disaccharides to monosaccharides and peptides to amino acids that can be directly absorbed, including enzymes like lactase, sucrase, maltase, and aminopeptidases.
Clinical Implications
The coordinated action of these hormones and enzymes ensures efficient breakdown and absorption of proteins, carbohydrates, and fats throughout the digestive tract, with proper treatment of exocrine pancreatic insufficiency (EPI) using pancreatic enzyme replacement therapy (PERT) being essential to improve outcomes and quality of life in patients with EPI 1.
Key Takeaways
- The use of PERT in patients with EPI improves outcomes and quality of life.
- Best Practice Advice 11: Once EPI is diagnosed, treatment with PERT is required to prevent complications related to fat malabsorption and malnutrition 1.
- Routine supplementation monitoring of fat-soluble vitamin levels and dietary modifications, such as a low-moderate fat diet with frequent smaller meals, are also recommended.
From the FDA Drug Label
When injected intravenously, sincalide stimulates gallbladder contraction and reduction in size. The evacuation of bile that results is similar to that which occurs physiologically in response to endogenous cholecystokinin. Sincalide also stimulates pancreatic secretion and intestinal motility causing pyloric contraction and slows gastric emptying Concurrent administration of sincalide with secretin increases both the volume of pancreatic secretion and the out-put of bicarbonate and enzymes.
The effects of the hormones and/or enzymes on macronutrient absorption are as follows:
- Secretin: Stimulates pancreatic secretion, which includes enzymes that aid in the digestion and absorption of macronutrients.
- CCK (Cholecystokinin): Stimulates gallbladder contraction, which releases bile into the small intestine to aid in fat absorption, and also stimulates pancreatic secretion.
- Enterokinase and Brush border enzymes: Not mentioned in the provided drug labels.
- The effect of Enterokinase and Brush border enzymes on macronutrient absorption cannot be determined from the provided information 2, 2. The FDA drug label does not answer the question for Enterokinase and Brush border enzymes.
From the Research
Hormones and Enzymes Affecting Macronutrient Absorption
- Secretin:
- CCK (Cholecystokinin):
- Regulates pancreatic enzyme secretion and growth, intestinal motility, satiety signalling, and inhibition of gastric acid secretion 5
- Stimulates gallbladder contraction, enabling bile acids to act simultaneously with pancreatic lipolytic enzymes 3
- Inhibits gastric motility and regulates satiety 3
- Plays a critical role in regulating food intake and diet-induced obesity 6
- Enterokinase:
- Activates trypsinogen, a pancreatic proenzyme, in the gut mucosa 3
- Brush Border Enzymes:
- No direct information available in the provided studies, however, it is known that brush border enzymes play a role in the final steps of carbohydrate and protein digestion, which can affect macronutrient absorption
Mechanisms of Action
- CCK stimulates pancreatic acinar cells through CCK-A receptors, leading to the secretion of digestive enzymes 3, 7
- Secretin receptors are expressed in the basolateral domain of several cell types, regulating epithelial functions in various organ systems 4
- CCK binding to its receptor CCK1R leads to vagal afferent activation, providing post-ingestive feedback to the hindbrain and regulating food intake 6