Secretin is a hormone that improves digestion while protecting the stomach and the gut. Abnormal secretin levels may be diagnostic of pancreatic disorders. It has a great impact on the fluid balance and levels of other digestive hormones while also benefiting the heart, brain, and lungs. Read on to learn more about the different roles that secretin plays in our bodies.

What is Secretin?

Secretin Definition

Secretin is a peptide hormone produced by gut cells (S cells of the small intestine) in response to gastric acid [1].

It was the first hormone to be discovered in the early 1900s and has been found in humans, mice, rats, dogs, pigs, and other mammals [1].

Secretin shows biological effects by interacting with secretin receptors. These are found in the heart, kidneys, stomach, and lungs [2].

Secretin Function

Secretin helps digestion by causing the stomach to make pepsin, prompting the liver to make bile, and causing the pancreas to make digestive juices [3].

In addition, this hormone is important for processes that are involved in water/fluid balance [4].

Finally, it also functions as a neurotransmitter (chemical messenger) in the brain [5].

Secretin Production

During digestion, food stimulates the release of a hormone called gastrin into the stomach. Gastrin causes stomach cells to produce stomach juice, a mixture of stomach acid and pepsin [6].

When the acidic contents from the stomach move into the intestine, the exposed cells release secretin [7, 8, 9].

Basically, secretin is released in response to a low pH (below 4.0) [10].

Secretin Health Effects

1) Secretin Protects the Gut

Secretin Reduces Acidity in the Gut

This hormone reduces increased stomach acid secretion after a meal to protect the gut tissue [11].

In a clinical study performed on 6 healthy humans, secretin inhibited stomach acid secretion stimulated by pentagastrin, an analog of natural gastrin [12].

This inhibitory effect was seen in rats and dogs as well [13, 2].

Secretin works by:

  • Increasing somatostatin, a hormone that decreases stomach acid secretion. Secretin increased somatostatin in rats and dogs [14, 2].
  • Increasing prostaglandin E2 (PGE2) [15, 14].
  • Acting through the vagus nerve to increase the secretin binding sites [16].
  • Decreasing gastrin production. Excessive production of gastrin and stomach acid causes stomach ulcers, damage to stomach lining cells, and bleeding [17, 18].

In H. pylori infection, some people develop ulcers while others don’t. H. pylori infection causes secretin deficiency and this lack of secretin may be the factor that causes peptic ulcers in these people [19].

Secretin also inhibits gut contractions, which reduces gut pressure and slows down the emptying of stomach liquids. This reduces the acidity in the gut, thus protecting the tissue [20].

Secretin reduced movement of the intestine and slowed down stomach emptying in humans, dogs, and, rats [21, 22, 23].

An acidic condition in the intestine increases secretin production. Secretin gives an inhibitory signal to the brain for reducing acid release and gut flow to protect the intestine [24].

In mice, high levels of secretin were associated with slower stomach emptying [25].

Secretin Increases Gut Mucus Production

Secretin protects stomach tissue by increasing mucus production.

It promoted mucus production in rat gut cells, where this mucus formed a protective gel layer [26].

Secretin increased mucus production via cAMP [27].

2) Secretin Aids Digestion

Secretin Increases Pancreatic Juice Production

Pancreatic enzymes are important for the digestion process in the gut (small intestine) [2].

Secretin increased pancreatic bicarbonate concentration by increasing the production of cAMP [2].

Secretin, together with another hormone, cholecystokinin or CCK, increased bicarbonate production in humans, dogs, and rats [28, 29, 30].

This resulted in increased pH of the pancreatic juice that helps pancreatic enzymes (trypsin, amylase, and lipase) digest food.

Secretin Promotes Liver Bile Production

Bile is produced by the liver and helps digest fat in the small intestine.

Secretin increases bile acid secretion. It increased bile flow in dogs, rats, and mice [2, 31, 32].

When secretin binds to secretin receptors, this increases cAMP production. cAMP increases bile release. Use of cAMP activators increased secretin-stimulated bile secretion in rats [33, 34].

Secretin Increases Pepsin Production in the Stomach

Secretin increases pepsin production in the stomach, which helps digestion by breaking down ingested proteins into smaller peptides [35].

3) Secretin Improves Water/Fluid Levels

At first, people thought secretin had diuretic properties. Early studies showed that it increased urine excretion in humans and dogs [36, 37, 38, 39].

However, later studies indicate that secretin actually has antidiuretic properties. Studies in rats showed that secretin acts on kidney receptors to decrease urine production through adenylate cyclase activation. Also, actions of secretin in mice lacking secretin receptors confirmed its antidiuretic action [40].

Angiotensin II is important in the fluid balance as it increases sodium reabsorption and water retention. Mice lacking secretin receptors showed reduced angiotensin II function [41].

In another study in rats, secretin showed a direct effect on kidney water reabsorption [42].

Secretin controls fluid balance by acting on different organs – the brain (hypothalamus), pituitary, and kidneys [42].

In secretin receptor-deficient mice, there was increased thirst, urination, and reduced water reabsorption [40].

Secretin Increases Thirst

Secretin acts on the brain’s secretin receptors to increase water intake. It works in combination with Angiotensin II. It increased water intake in mice when administered directly to the brain [43].

In rats, secretin increased water intake by activation of oxytocin (OXT)-secreting neurons in the brain [44].

4) Secretin May Improve Social Behavior

Secretin acts as a neurotransmitter in the brain.

Secretin-deficient mice show reduced hippocampal function and impaired social behavior [45, 46].

Oxytocin plays an important role in social behavior. Secretin increased oxytocin release in the brain and, thus, increased social behavior in rats [47].

5) Secretin May Improve Motor Coordination

Secretin has a direct action on the Purkinje neurons in the cerebellum of the brain. Purkinje neurons play a major role in motor coordination and learning.

Mice lacking secretin have reduced motor coordination and motor learning ability [48].

In another study, administration of secretin through the nose improved motor behavior and reduced hyperactivity in mice [49].

6) Secretin May Increase the Growth of New Neurons and Synapses

Secretin acts as a neurotransmitter in the brain and it has a growth-helping effect on the neurons in mice [3].

Secretin-deficient mice had less new neurons, as more neuron-producing cells were dying [50].

In another study, secretin-deficient mice showed reduced activity of the neuronal synapses in the hippocampus, indicating a role for secretin in brain function and development [45].

7) Secretin May Improve Heart Function

Secretin increases heart activity by increasing cAMP.

This hormone increased blood volume output and heart rate in cats and dogs [51, 3].

In another study, secretin increased the heart function and blood flow in pigs by acting through beta-adrenoceptors and by increasing nitric oxide release [52].

8) Secretin May Increase Air Supply in the Lungs

Secretin receptors are also detected in human lungs [53].

In 16 human lung tissue donors, secretin relaxed airway smooth muscles (it caused bronchorelaxation), suggesting a helpful role in increasing air supply in the lungs [53].

It may, therefore, be beneficial in asthma and allergies.

9) Secretin May Reduce Appetite

The hypothalamus plays an important role in appetite control. It is where the feeding and satiety centers are [54].

Secretin activated the appetite control center in the hypothalamus of the brain and reduced insulin-stimulated fat production in rats [55, 2].

In another study, secretin in the amygdala reduced glucose sensitive neuronal activation and also decreased cumulative food intake in rats [56].

10) Treatment with Secretin May Helps with Schizophrenia

Schizophrenia causes major cognitive and motor disabilities. One such disability is associative learning. It can be evaluated by eye blinking activity. In a double-blind clinical study of 25 patients with schizophrenia, secretin given under the skin improved eye motor activity better than placebo treatment [57].

However, in another study (RCT) of 22 patients with schizophrenia treated with intravenous secretin, there was no significant difference between secretin and placebo, although some individuals did show clinically meaningful improvement [58].

Secretin Negatives

1) Secretin May Contribute to Liver Damage in Cholestasis

During cholestasis (impaired bile flow), secretin receptors get increased. Increased secretin activity leads to increased bile duct cell growth and ultimately liver damage.

In mice with cholestatic liver injury, secretin receptor blockers reduced bile duct cell growth and liver damage [59].

2) Secretin Exacerbates Zollinger-Ellison Syndrome (ZES)

ZES is a condition that causes excessive gastrin production and damaging effects to the stomach tissue. Secretin significantly stimulated gastrin release from the gastrinoma cells of a patient with ZES [60].

In another study, secretin and calcium increased blood gastrin levels in eight patients with ZES and eighteen patients with duodenal ulcers [61].

Secretin treatment increased gastrin levels is Zollinger-Ellison patients, but reduced gastrin levels in duodenal ulcer patients. Thus, the secretin challenge test is a very useful tool to differentiate between ZES vs. non-ZES patients [61].

3) Treatment with Secretin Does Not Show Any Benefits in Autism

Cortex, a brain region important for cognitive function and environmental awareness, has secretin receptors. Use of secretin in the rat brain showed activation of the cortex [62]. Therefore, people thought that secretin may help in autism.

In a single clinical study, 3 children with autism treated with secretin for 5 weeks showed a significant improvement in the symptoms, behavior, eye contact, and language [63].

But since then, in over 14 clinical studies with over 900 autism patients, secretin treatment did not show any effectiveness [64, 65, 66].

Drugs That Decrease Secretin

Lafutidine, a drug used to treat stomach ulcers, reduces secretin levels. A single oral dose of Lafutidine reduced blood secretin levels in healthy human volunteers [67].

Omeprazole, an anti-acid reflux drug, reduces secretin levels. In a crossover study with 10 healthy men, omeprazole reduced secretin levels immediately after a meal [68].

Secretin and Other Hormones


Gastrin is a hormone that stimulates stomach acid production [6].

Cells of the stomach, intestine, and pancreas release gastrin.

Secretin suppressed food-stimulated gastrin secretion and stomach acid production in 22 human subjects [17].

However, gastrin also inhibits secretin action.

It inhibited release of secretin in rats by interacting with CCK-B receptors in liver cells. This reduced secretin receptors and related cAMP levels in rats [7].

Cholecystokinin (CCK)

Gut cells release CCK. This hormone is responsible for the stimulation of the gallbladder and releases bile into the intestine for digestion of fats and proteins. It also stimulates the pancreatic enzyme secretion.

Secretin increased effects of CCK on pancreatic bicarbonate secretion in humans, dogs, and rats [69, 29].


Secretin stimulates the release of insulin from the pancreas after glucose consumption. Six human subjects receiving glucose increased blood secretin and produced insulin [70].

In a clinical study, secretin played a dual role in insulin secretion in healthy humans. It directly increased insulin secretion and also prolonged the effect of insulin [71].

In another study in humans, intravenous secretin increased insulin release, immediately reaching high levels [72].

Secretin Stimulation Test

This is a test that is used to diagnose pancreas-related disorders and diseases such as inflammation or tumors. It is a measurement of the ability of the pancreas to respond to secretin by releasing substances like bicarbonate and trypsin into the pancreatic juice within the intestine [73].

In this test, you will receive secretin through the nose or throat via a tube (that goes into the small intestine and stomach), or directly into a vein. After 1 – 2 hours, blood levels of pancreatic secretions are evaluated as a measurement of pancreatic function [R, 74].

Abnormal levels of pancreatic secretions would suggest that there are problems in the pancreas.

Available Secretin

FDA-approved secretin (by injection) is a diagnostic agent for stimulating the pancreas to help detect pancreatic problems. Secretin is given only by or under the supervision of a medical doctor, such as a diagnostic for illnesses. [75].

About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PhD (Ecological Genetics)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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