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Pancreatic Polypeptide: Function & Associated Diseases

Written by Joe Cohen, BS | Last updated:
Nicole Craven
Medically reviewed by
Nicole Craven, MD | Written by Joe Cohen, BS | Last updated:

Pancreatic polypeptide is a peptide secreted by your pancreas. It is thought to affect your brain, your behavior, and your digestive system. It is also believed to be involved in anorexia and obesity. Pancreatic polypeptide levels play a role in appetite and weight and could even be a sign of cancer or diabetes. Read on to learn more.

What Is Pancreatic Polypeptide?

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The pancreatic polypeptide is a hormone produced by the pancreas and is involved in digestion [1].

Pancreatic polypeptide is secreted together with insulin, the glucose-lowering hormone produced by the pancreas [2].

The pancreas quickly releases pancreatic polypeptide after a meal and its levels remain elevated for 4 to 6 hours. Its secretion is stimulated most strongly by eating protein and fat [3].


The pancreatic polypeptide is secreted by the pancreas along with enzymes and hormones involved in digestion [4].

Hormones are produced in regions of the pancreas called islets of Langerhans. These islets contain five different types of cells (alpha, beta, delta, epsilon, and PP or gamma), each of which produces a different hormone involved in blood sugar levels and eating [5].

PP cells produce pancreatic polypeptide for use in the pancreas and target organs such as the brain [6].


Pancreatic polypeptide targets many organs. First, it works upon the brain via the vagus nerve, which connects the brain to the lungs, heart, and digestive system. This sends information about hunger and satiety to the brain [7, 8].

The pancreatic polypeptide causes satiety in several ways. In the brain, it reduces appetite. In the digestive system, it decreases the rate at which food moves through the digestive system producing a longer lasting  feeling of fullness [9].

This polypeptide also affects several organs in the digestive system. The pancreatic polypeptide relaxes the gallbladder. This stops the release of bile from the gallbladder and slows digestion [10, 11].

It also reduces the secretion of other substances, such as digestive enzymes and pancreatic bicarbonate, by the pancreas [12].

Finally, the polypeptide controls the rate at which food moves through the digestive system [8].

The pancreatic polypeptide sends signals through different receptors, including Y1, Y2, Y4, and Y5 [13]. The Y1 and Y5 receptors stimulate the appetite, while the Y2 and Y4 receptors repress it [14].

Though its function to reduce appetite may sound appealing, you can see it also hinders the digestive process of bile and other enzymes that is essential for gut health.


Motilin is a peptide produced in the small intestine. Like pancreatic polypeptide, motilin is a hormone that controls the digestive system in an opposite manner than pancreatic polypeptide [15, 16].

First, its levels decrease after eating, while pancreatic polypeptide is released after eating [17].

Pancreatic polypeptide makes the gallbladder relax; motilin makes the gallbladder, stomach, and the intestine contract [10, 16, 15].

The Gut-Brain Axis

Pancreatic polypeptide is one of the hormones involved in the brain-gut axis. Other hormones include insulin, histamine, and cholecystokinin [18, 19].

These hormones act on organs in the digestive system, but they do not do this directly. In the brain-gut axis, hormones produced in the digestive system use the nerves and brain to send signals back to the digestive system [19].

Many of the hormones in the brain-gut axis have opposite effects as a controlled feedback system [19].

For example, a hormone called leptin causes the feeling of fullness, while insulin and ghrelin work together to likely increase hunger signals [20, 21].

The levels of pancreatic polypeptide and the other hormones are controlled by a system of feedback loops or checks that ensure that food is being eaten at the right time and digestion is taking place at the right speed [22].

High Levels of Pancreatic Polypeptide

May Help Prevent Obesity

One benefit of having high levels of pancreatic polypeptide is a tendency to maintain a lower body weight, according to animal studies. Pancreatic polypeptide also has anorexigenic effects through its role in glucose homeostasis [23, 24].

Hormones in the blood control appetite and food consumption. These hormones either work in the long term by regulating body weight over weeks or months or short term by affecting appetite over the span of a day [25].

Pancreatic polypeptide works in the short term. Though this means that the polypeptide only directly affects appetite over the course of a day, the food intake of many days combined can cause long-term effects [26, 3].

When pancreatic polypeptide was injected directly into mice stomachs, their food consumption decreased, and they used more energy. This prevented obesity [27].

Similarly, mice that produced excess pancreatic polypeptide consumed less food and had lower body weights [23]. Additional studies will be needed to determine if it can play a similar role in humans.

Diseases Associated with High Levels of Pancreatic Polypeptide

1) High PP Levels And Anorexia

People with anorexia experience increased feelings of fullness and reduced hunger. This is caused by abnormal hormone signaling (transmission). In anorexia, food takes longer to pass through the digestive system. This increased digesting time is one result of pancreatic polypeptide transmission. It causes increased feelings of fullness [28, 29].

In one study, 13 included anorexic women had increased levels of pancreatic polypeptide. This was true of people with anorexia regardless of weight status, suggesting that it was not merely a result of weight loss or malnutrition [29].

The abnormally high levels of pancreatic polypeptide did not decrease after anorexic patients begin to eat normally again. Furthur research will be needed to determine if this could be a cause for the high rates of relapse in people with anorexia [29].

2) High PP Levels Are Associated with Acute Pancreatitis

Acute pancreatitis is an inflammatory disease of the pancreas. In acute pancreatitis, the pancreas’ own digestive enzymes destroy parts of the pancreas (autodigestion) [30].

Early diagnosis is important so that the disease can be treated before complications occur. To quickly diagnose this disease, there must be a marker that (1) changes soon after pancreatitis begins and (2) remains changed as the disease progresses [30].

Pancreatic polypeptide may be a good marker for the diagnosis of acute pancreatitis. In animals, pancreatic polypeptide levels in the blood increase quickly after the disease begins and stay elevated [31].

However, there is some debate over whether this is true in humans [32, 33].

Additionally, it appears that pancreatic polypeptide could be useful in treating acute pancreatitis. Secretion of hormones out of the duct of the pancreas significantly worsens pancreatitis, and pancreatic polypeptide reduces this secretion [30].

3) High PP Levels Are Associated with Neuroendocrine Tumors

Pancreatic neuroendocrine tumors are cancerous growths involving the cells of the pancreas that produce hormones. These tumors can be of two types: functioning and nonfunctioning [34, 35].

Functioning tumors have symptoms that are caused by the abnormal secretion of hormones. Nonfunctioning tumors can have abnormal hormone levels too, but the hormones do not cause symptoms [35].

Different tumors have distinct hormone abnormalities. Pancreatic polypeptide is one of the biomarkers used to tell different pancreatic tumors apart [34].

High levels of pancreatic polypeptide are seen in several neuroendocrine tumors, such as carcinoid tumors and pancreatic polypeptidomas. Carcinoid tumors are a group of tumors of the neuroendocrine cells that can appear in a variety of different organs, especially the lungs and the digestive tract [36].

Meanwhile, pancreatic polypeptidomas are tumors that produce large amounts of pancreatic polypeptide but have few other symptoms [37].

One review determined that pancreatic polypeptide can be used to identify a tumor when combined with other tumor markers [38].

4) High PP Levels And Other Cancers

Other pancreatic tumors that are not involved with the hormonal system are also associated with high levels of pancreatic polypeptide, as are tumors of the bile duct [39].

Tumors outside of the digestive system also show differences in pancreatic polypeptide levels. For example, patients with other advanced cancers, such as lung cancer, have elevated pancreatic polypeptide levels [40].

It is possible that the pancreas secretes more pancreatic polypeptide as a response to the cancer. However, it is also possible that the tumors themselves produce pancreatic polypeptide [40].

The presence of pancreatic polypeptide in different tumors has spurred research into determining if the polypeptide could be used as a new marker for diagnosing tumors. This would increase speed and accuracy in the diagnosis of cancer [40].

The study of pancreatic polypeptide could even potentially lead to new cancer treatments [39].

5) High PP Levels And Arthritis

Arthritis and autoimmune rheumatoid arthritis cause inflammatory pain and swelling in the joints.

One study showed the levels of pancreatic polypeptide were elevated in 54% of people with rheumatoid arthritis, as well in people with similar autoimmune inflammatory diseases such as scleroderma, mixed connective tissue disease, and temporal arteritis. The magnitude of the increase corresponds to the degree of inflammation [41].

Not only is the amount of pancreatic polypeptide increased in people with rheumatoid arthritis, it is also increased in people who are at risk for the disease [42].

However, not every similar disease is connected to pancreatic polypeptide. Systemic sclerosis, a connective tissue disease just like arthritis, did not cause a change in the levels of pancreatic polypeptide in fifteen patients [43].

Low Levels of Pancreatic Polypeptide

Having low levels of pancreatic polypeptide in the blood implies that a person likely does not have acute pancreatitis or one of several types of hormonal tumors [31, 36].

Since the secretion of pancreatic polypeptide reduces hunger, having low levels of this polypeptide implies that a person is less likely to be malnourished or to exhibit symptoms of anorexia [29].

Diseases Associated With Low Levels of Pancreatic Polypeptide

1) Low PP Levels And Chronic Pancreatitis and Diabetes

Chronic pancreatitis is the long-term inflammation of the pancreas. It does not heal with time and can worsen and result in complications, such as pancreatogenic diabetes and glucose intolerance [44, 45, 46, 47].

Diabetes in pancreatitis occurs because the inflammation destroys the cells that produce insulin. In pancreatogenic diabetes, the cells that produce pancreatic polypeptide and other hormones are destroyed as well [48].

It is important to be able to distinguish pancreatogenic diabetes from type 1 or type 2, since the treatment is different. This is done by testing pancreatic polypeptide levels: low levels of pancreatic polypeptide implies pancreatogenic diabetes [48].

2) Low PP Levels and Obesity

Prader-Willi Syndrome is a complex disorder that causes, among other symptoms, an insatiable appetite. Individuals suffering from this disorder tend to be obese, and many die from complications resulting from obesity [49].

People with Prader-Willi syndrome release less pancreatic polypeptide after eating than do people without the disorder. One study showed smaller increases or no increase in pancreatic polypeptide levels after eating in six out of seven people with Prader-Willi syndrome [50].

The failure to experience fullness is caused by a deficiency in the release of pancreatic polypeptide [51].

Additionally, even obese people without this disorder have a reduced pancreatic polypeptide response after eating [52].

Conversely, the peripheral administration (injection into the veins) of pancreatic polypeptide to 16 people prone to obesity suppresses the tendency to gain excessive weight by reducing food consumption by 12% in human patients [51]. However, this was a very small study involving only 16 people. Further work needs to be done before firm conclusions can be drawn from it.

3) PP and Bone Density

The body is always building bones up and then breaking them down again. It is important to maintain a balance between this production and the destruction of bone tissue. If more bone is destroyed than is created, bones will be fragile and easily broken [53].

Cells that form bone are called osteoblasts, while cells that reabsorb bone are called osteoclasts. Both of these cells are controlled by hormones, and pancreatic polypeptide is one of those hormones [53, 54].

Pancreatic polypeptide affects the creation of bone-producing cells, which in turn could increase the number of these cells [54].

Some studies suggest that preventing pancreatic polypeptide from working reduces the number of bone-producing cells. However, this has been contradicted in further studies [53].

Things That May Effect Pancreatic Polypeptide Levels

Increasing PP

One way to potentially increase the release of pancreatic polypeptide is to exercise. Exercise results in an energy deficit, which in turn stimulates the release of pancreatic polypeptide. In thirteen obese people, pancreatic polypeptide levels increased by 38% after fifteen days of exercise [55]. Once again, it is important to remember that this was a single small study in thirteen people and only lasted for fifteen days.


Cholecystokinin is a hormone produced in the intestine. It causes the gallbladder to contract and stimulates secretion from the pancreas. Just like pancreatic polypeptide, cholecystokinin increases fullness and reduces food consumption [56, 57].

The early research on wether cholecystokinin can release more pancreating polypeptide is mixed. Early research showed that cholecystokinin may cause the release of pancreatic polypeptide. In 6 healthy volunteers, after cholecystokinin infusion, the levels of pancreatic polypeptide in the blood were significantly higher than normal. The levels returned to normal 45 minutes after the infusion [58].

However, another study involving eighteen healthy people showed no change in pancreatic polypeptide levels after injection of cholecystokinin into the blood [59].

Decreasing PP

There is some debate on the usefulness and benefit of a reduction in the levels of pancreatic polypeptide in people, such as those suffering from anorexia. Talk with your doctor before making any major changes to your day-to-day routine [60].

Pancreatic Polypeptide Tests

1) PP Blood Test

The pancreatic polypeptide test measures the levels of pancreatic polypeptide in the blood. The level is often elevated if the patient has a tumor of the pancreas, diabetes, duodenal ulcer, or has recently eaten [61, 62].

This test is mainly used in the diagnosis of pancreatic tumors, even in early stages. Because of this, it is mostly performed on people that have jaundiced (yellow) skin, weight loss, or belly pain characteristic of pancreatic or bile duct disease [63].

2) Vagal Nerve Function Test

It is possible that a damaged vagus nerve can be tested by measuring PP levels instead of more invasive methods.

The vagus nerve, which carries information between the brain and digestive system can be damaged during gastric surgery [7]. Vagus nerve damage can cause bloating, pain, and other symptoms.

Traditionally, damage in the vagus nerve has been tested by stimulating the activity of the nerve or injecting the patient with insulin, but the first method is invasive and the second can result in dangerous complications [64, 65].

A safer and easier way to test for problems with the vagus nerve is to measure the levels of pancreatic polypeptide. After chewing food, the amount of pancreatic polypeptide in the blood should rise [65].

If the level does not increase, or only increases slightly, then the vagus nerve has been damaged [66].

About the Author

Joe Cohen, BS

Joe Cohen, BS

Joe Cohen flipped the script on conventional and alternative medicine…and it worked. Growing up, he suffered from inflammation, brain fog, fatigue, digestive problems, insomnia, anxiety, and other issues that were poorly understood in traditional healthcare. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. Based on his own health success, he went on to found SelfDecode, the world’s first direct-to-consumer DNA analyzer & precision health tool that utilizes AI-driven polygenic risk scoring to produce accurate insights and health recommendations. Today, SelfDecode has helped over 100,000 people understand how to get healthier using their DNA and labs.
Joe is a thriving entrepreneur, with a mission of empowering people to take advantage of the precision health revolution and uncover insights from their DNA and biomarkers so that we can all feel great all of the time.


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