Pancreatic polypeptide affects your brain, your behavior, and your digestive system. It is involved in anorexia and obesity, so it can potentially be used for weight loss. Your levels of pancreatic polypeptide determine your appetite and weight and could be a sign of cancer or diabetes. Read on to learn more about how pancreatic polypeptide affects you.

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 [6].

The hormones produced by the pancreas are released into the bloodstream, where they circulate and affect their target organs [5, 7].


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 [8, 9].

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. This causes the feeling of fullness to last longer [10].

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 [11, 12].

It also reduces the secretion of other substances, such as digestive enzymes and pancreatic bicarbonate, by the pancreas [13].

Finally, the polypeptide controls the rate at which food moves through the digestive system [9].

The pancreatic polypeptide sends signals through different receptors, including Y1, Y2, Y4, and Y5 [14]. The Y1 and Y5 receptors stimulate the appetite, while the Y2 and Y4 receptors repress it [15].


Motilin is a peptide produced in the small intestine. Like pancreatic polypeptide, motilin is a hormone that controls the digestive system [16, 17].

Motilin is the opposite of pancreatic polypeptide in several ways. First, its levels decrease after eating, while pancreatic polypeptide is released after eating [18].

Pancreatic polypeptide makes the gallbladder relax; motilin makes the gallbladder, the stomach, and the intestine contract [11, 17, 16].

Motilin directly affects pancreatic polypeptide. In dogs, it stimulates the release of pancreatic polypeptide. Pancreatic polypeptide does not affect the release of motilin [19].

The Gut-Brain Axis

Pancreatic polypeptide is one of the hormones involved in the brain-gut axis. Other hormones include insulin, histamine, and cholecystokinin [20, 21].

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 [21].

Many of the hormones in the brain-gut axis have opposite effects [21].

For example, a hormone called leptin causes the feeling of fullness, while insulin stimulates the release of a hormone that causes hunger [22, 23].

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 [24].

Benefits of High Levels of Pancreatic Polypeptide

Prevents Obesity

One benefit of having high levels of pancreatic polypeptide is a tendency to maintain a lower body weight [25].

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 [26].

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 [27, 3].

When pancreatic polypeptide was injected directly into mice stomachs, their food consumption decreased, and they used more energy. This prevented obesity [28].

Similarly, mice that produced excess pancreatic polypeptide consumed less food and had lower body weights [25].

Diseases Associated with High Levels of Pancreatic Polypeptide

1) High PP Levels Can Cause 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 [29, 30].

In a study of 13 anorexic women, they had increased levels of pancreatic polypeptide. This was true whether the people with anorexia were thin, meaning that it was not merely a result of weight loss or malnutrition [30].

The abnormally high levels of pancreatic polypeptide did not decrease after anorexic patients begin to eat normally again. This could be a cause for the high rates of relapse in people with anorexia [30].

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) [31].

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 [31].

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 [32].

However, there is some debate over whether this is true in humans [33, 34].

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 [31].

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 [35, 36].

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 [36].

Different tumors have distinct hormone abnormalities. Pancreatic polypeptide is one of the biomarkers used to tell different pancreatic tumors apart [35].

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 [37].

Meanwhile, pancreatic polypeptidomas are tumors that produce large amounts of pancreatic polypeptide but have few other symptoms [38].

One review determined that pancreatic polypeptide can be used to identify a tumor when combined with other tumor markers [39].

4) High PP Levels Are Linked to 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 [40].

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 [41].

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 [41].

The presence of pancreatic polypeptide in different tumors means that the polypeptide could be used as a new marker for diagnosing tumors. This would increase speed and accuracy in the diagnosis of cancer [41].

The study of pancreatic polypeptide could even potentially lead to new cancer treatments [40].

5) High PP Levels Are Linked to Arthritis

Arthritis is inflammation of the joints and causes pain, swelling, and other symptoms. Rheumatoid arthritis is also associated with increased death rates and heart problems [42].

The levels of pancreatic polypeptide are elevated in 54% of people with rheumatoid arthritis, as well in people with similar diseases such as scleroderma, mixed connective tissue disease, and temporal arteritis. The magnitude of the increase corresponds to how severe the inflammation is [43].

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

Hormones like pancreatic polypeptide may be connected to the heart problems experienced by people with rheumatoid arthritis. Pancreatic polypeptide levels are elevated in people with heart 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 [44].

6) High PP Levels Are Linked to Watery Diarrhea Syndrome

People with watery diarrhea syndrome may also have hypokalemia (low blood potassium), hyperglycemia (high blood sugar), hypercalcemia (high levels of calcium in the blood), and low blood pressure [45].

Watery diarrhea syndrome is a symptom of hormone-secreting tumors [45].

One case study described a patient who had watery diarrhea syndrome and a pancreatic tumor that produced the pancreatic polypeptide, insulin, and other hormones [46].

Another case study involved a person who had no pancreatic tumor but had many more pancreatic polypeptide-producing cells than normal [47].

In an additional study of four people with pancreatic tumors and watery diarrhea syndrome, three of the patients’ tumors had cells that produced pancreatic polypeptide [48].

However, in rats, pancreatic polypeptide does not have an effect on how much water or electrolytes are absorbed in the intestines. This suggests that pancreatic polypeptide levels do not cause watery diarrhea syndrome [49].

Benefits of Low Levels of Pancreatic Polypeptide

Having low levels of pancreatic polypeptide in the blood means that a person likely does not have acute pancreatitis or one of several types of hormonal tumors [32, 37].

Since the secretion of pancreatic polypeptide reduces hunger, having low levels of this polypeptide means that a person is less likely to be malnourished or to exhibit symptoms of anorexia [30].

Diseases Linked to Low Levels of Pancreatic Polypeptide

1) Low PP Levels Are Linked to Chronic Pancreatitis and Diabetes

Chronic pancreatitis is 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 [50, 51, 52, 53].

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 [54].

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 means pancreatogenic diabetes [54].

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 [55].

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 [56].

The failure to experience fullness is caused by a deficiency in the release of pancreatic polypeptide [57].

Additionally, even obese people without this disorder have a reduced pancreatic polypeptide response after eating [58].

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 [57].

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 destruction of bone tissue. If more bone is destroyed than is created, bones will be fragile and easily broken [59].

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 [59, 60].

Pancreatic polypeptide affects the creation of bone-producing cells, which in turn could increase the number of these cells [60].

Some studies suggest that preventing pancreatic polypeptide from working reduces the number of bone-producing cells. However, this has been contradicted in further studies [59].

How to Change Your Pancreatic Polypeptide Levels

Increasing PP

One way to 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 [61].

The injection of histamine temporarily increases levels of pancreatic polypeptide by 86% in humans [62]. Histamine is a chemical that is released by the body in response to injury or inflammation [63].

However, excess histamine can cause symptoms similar to an allergic reaction. Congestion, headache, and elevated heart rate can be caused by too much histamine [63].

Increasing PP with Cholecystokinin

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 [64, 65].

Some research has shown that cholecystokinin causes 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 [66].

However, another study involving eighteen healthy people showed no change in pancreatic polypeptide levels after injection of cholecystokinin into the blood [67].

Decreasing PP

Some people, such as those suffering from anorexia, could benefit from a reduction in the levels of pancreatic polypeptide [68].

One way to decrease the amount of pancreatic polypeptide in the blood is through atropine. Atropine is a drug naturally produced by the deadly nightshade plant belladonna [69, 70].

In humans, atropine blocks the release of pancreatic polypeptide at the same time that it reverses the effects that pancreatic polypeptide has on the digestive system [69, 71].

However, atropine can cause side effects including altered mental state, elevated heart rate, and an inability to sweat [70].

Pancreatic Polypeptide Tests

1) PP Blood Test

The pancreatic polypeptide test measures the levels of pancreatic polypeptide in the blood. The level is elevated if the patient has a tumor of the pancreas, diabetes, duodenal ulcer, or has recently eaten [72, 73].

This test is mainly used in the diagnosis of pancreatic tumors. Because of this, it is mostly performed on people that have jaundiced (yellow) skin, lost weight, or belly pain, since these are symptoms of tumors of the pancreas [74].

2) Vagal Nerve Function Test

Some stomach surgeries run a risk of damaging the vagus nerve, which carries information between the brain and the heart, lungs, and digestive system [8].

Vagus nerve damage can cause bloating, pain, and other symptoms, so it is important to be able to test its function [75].

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 [76, 75].

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 [75].

If the level does not increase, or only increases slightly, then the vagus nerve has been damaged [77].

Irregular Pancreatic Polypeptide Levels?

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