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Amylin: Function, Associated Diseases, & Drugs

Written by Carlos Tello, PhD (Molecular Biology) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Last updated:

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Diabetes is commonly associated with insulin, but amylin is another key hormone that also helps control blood sugar. In addition to diabetes, this hormone is linked to Alzheimer’s, osteoporosis, and kidney disease. Read on to find out more about this hormone and why amylin-mimicking drugs can be useful for diabetes and weight loss.

What Is Amylin?

Insulin has the daunting task of keeping blood sugar levels in balance. However, it doesn’t do it alone. Amylin, also known as islet amyloid polypeptide (IAPP), is a hormone produced mainly by the pancreatic beta cells and that gets released into the blood together with insulin [1].

After a meal, the pancreas responds to the rising blood sugar level by releasing these two hormones. The amount of insulin released is 20 times higher than amylin, but they follow the same rise and fall pattern seen during periods of eating and fasting [2, 3].

Amylin may also be produced in the brain (hypothalamus), lungs, and gut based on animal research. However, this has yet to be confirmed in humans [4, 5].

Besides controlling blood sugar, amylin may also play important roles in controlling energy usage, blood pressure, and bone metabolism.

Normal Levels

Lab results are commonly shown as a set of values known as a “reference range”, which is sometimes referred to as a “normal range”. A reference range includes the upper and lower limits of a lab test based on a group of otherwise healthy people.

Your healthcare provider will compare your lab test results with reference values to see if any of your results fall outside the range of expected values. By doing so, you and your healthcare provider can gain clues to help identify possible conditions or diseases.

Some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range in the app – as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.

However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.

Have in mind that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly low/high may not be of medical significance, as this test often varies from day to day and from person to person.

Blood amylin levels are normally measured through ELISA immunoassays that are not included in general blood tests [6, 7].

In a study of 79 people, healthy subjects had a normal blood amylin level of 6.95 pmol/L (range of 4.45-9.45 pmol/L) [6].

Those with obesity, high blood pressure, and a family history of insulin resistance have higher amylin levels. Type 2 diabetic patients had an average of 8.48 pmol/L (range of 5.67-11.29 pmol/L) [8].

Functions and Health Benefits

Amylin helps control blood glucose. When it is working properly, the body needs less insulin. It contributes to glucose control in 3 main ways (benefits 1-3) but may also improve leptin and bone metabolism or enhance cognition and brain function.

Amylin exerts its effect by binding to the amylin receptors. Each amylin receptor is a combination of a calcitonin receptor (CTR) and one or several receptor activity-modifying proteins (RAMPs) [9].

1) Slowing Down Digestion

Amylin in the brain signals the stomach to slow food movement into the small intestine (gastric/stomach emptying), which helps feel full and satiated [10].

Also, when carbohydrates stay in the stomach for longer, they get broken down to glucose and are absorbed more slowly and gradually.

Diabetes patients have a faster rate of stomach emptying and glucose absorption due to a lack of amylin [11].

How amylin slows stomach emptying is not yet understood, but studies indicate the vagus nerve plays a key role [5].

2) Blocking Glucagon

After a meal, amylin suppresses the release of the hormone glucagon. Glucagon (in stress, hunger, or diabetes) raises blood glucose by releasing it from liver stores into the blood [12].

In rats, blocking amylin function resulted in higher glucagon levels [13].

3) Promoting Satiety

We stop eating when we feel “full”. Amylin acts as a satiation factor (inducing a feeling of “fullness”) after food intake by activating amylin/calcitonin receptors in the brain [14].

In a study, rats ate less food within a few minutes after having been injected with amylin [15].

In several clinical trials on both healthy and overweight people, injection with an amylin drug (pramlintide) reduced food intake [16, 17].

The amylin/calcitonin receptor is found in a region of the brain called area postrema. Removing this area blocks the effects of amylin. Similarly, infusing an amylin blocker into this area increased food intake in rats [18, 19, 20].

Although it may also work by activating other brain areas, the exact mechanisms are yet to be studied [5, 9].

Finally, amylin also reduced food-related motivation behaviors in animals, suggesting that, apart from causing a feeling of fullness, it also reduces the rewarding effects of food [9].

4) Increasing Sensitivity to Leptin

Leptin is a hormone produced by fat cells that stimulates fat burning while inhibiting hunger. Many obese people are leptin-resistant even if they have high leptin levels from having more fat cells [21].

In a clinical trial on 177 obese/overweight subjects, an analog of amylin (metreleptin) alone did not result in weight loss. However, administering it with an amylin drug (pramlintide) resulted in significant weight loss [21].

5) Helping Control Energy Expenditure And Body Weight

The pancreas secretes amylin in proportion to increased body weight. It can reduce eating by enhancing the effects of “fullness” signals (such as CKK) [22, 23].

In several animal studies, long-term amylin administration decreased body weight and fat gain, while blocking amylin activity increased body fat. Therefore, amylin can contribute to the balance of body weight [15, 24].

Similar to humans, brown adipose tissue (BAT) contributes to the control of total energy usage in rats. Amylin increases BAT activity. Mice with increased activity of the RAMP1 protein (part of the amylin receptor family) had reduced body weight and fat mass, and increased energy expenditure and body temperature [25, 26, 27].

6) Helping Maintain Bone Density

Amylin is a member of the calcitonin family of hormones and can affect bone formation. It also affects bone reabsorption through an unknown receptor [28].

In diabetic mice, amylin exerted bone remodeling effects and helped with bone growth. Inactivating amylin led to low bone mass [29, 28].

Amylin deficiency in mice also caused osteopenia (low bone mass and strength). Sex hormones, growth factors, or cytokines and amylin can interact and cause abnormal bone formation in male mice. Thus, amylin deficiency’s effects on bone growth may be sex-dependent [30].

7) Improving Cognitive Function

In humans, lower amylin levels are associated with cognitive defects, like dementia and Alzheimer’s. Amylin can reduce energy intake, which is associated with a better cognitive ability [5, 31].

In a study of 370 people, amylin drug (pramlintide) administration improved memory and decreased oxidative stress [32].

However, increased amylin may also contribute to defects seen in Alzheimer’s by increasing inflammatory cytokines such as IL-6 [33].

8) Antipsychotic Effects

Amylin injections in certain parts of the rat brain (accumbens shell) reduced psychotic behavior, suggesting the potential of amylin receptors as therapeutic targets for antipsychotic drug development [34].

Dual (Both Positive and Negative) Effects

Affecting Blood Pressure

CGRP receptor activity is responsible for most of amylin’s actions on blood pressure and the heart [35].

In rats, amylin injection decreased blood pressure. However, this effect was not seen in a 12-month study in humans. Pramlintide (an amylin drug) did not significantly change blood pressure [36, 37].

In rats with high blood pressure, their amylin binding sites were denser compared to normal rats. Thus, amylin and its receptors may contribute to the development or maintenance of high blood pressure [38].

Negative Effects

Forming Plaques

Amylin can self-aggregate (combine together) and eventually form amyloid plaques [39].

High amylin levels contribute to the early processes of amyloid formation in the brain and spinal cord. In turn, low amylin levels are more strongly associated with the late stages of amyloid disorders [40].

The brain tissues of type 2 diabetic rats had increased amylin and amyloids, which plays a role in impairing brain function and Alzheimer’s [39].

Amyloids are hard to study because unlike in humans, amylin does not form plaques in rats [40].

Diseases Linked to Amylin

The following conditions are commonly associated with abnormally low or high amylin levels, but this symptom alone is insufficient for a diagnosis. Work with your doctor to determine what underlying condition is altering your amylin levels and develop a plan to properly treat it.

Low Amylin

1) Reduced Bone Strength/Osteoporosis

Amylin is a member of the calcitonin family of hormones and can affect bone formation. It stimulates the spread of cells that help with bone formation and absorption [41].

Low amylin is associated with lower bone mineral density, meaning lighter and weaker bones. The amylin level was a significant predictor of bone mineral density in a study of 31 healthy women and women with anorexia [42].

In another study of 52 healthy, diabetic, and osteoporosis patients, osteoporosis patients had lower amylin levels. These low levels may contribute to osteoporosis development [41].

The bone loss observed in type 1 diabetes patients has been associated with amylin deficiency [43].

Amylin-deficient mice also had lower bone mass [44].

2) Type 1 Diabetes

Amylin production is lower or nonexistent in the pancreas of type 1 diabetes patients. This is probably because the body’s own immune system destroys amylin and insulin-producing pancreatic cells in people with type 1 diabetes [45, 46].

Studies in people with type 1 diabetes or insulin-treated type 2 diabetics found that amylin was still not produced after a meal in these conditions [47, 3].

Both Low and High Amylin

1) Type 2 Diabetes

Amylin levels in type 2 diabetes depend on the progression of the disease. In earlier stages levels are high, however, as the disease progresses and the beta-cells fail, amylin levels also fall [5].

The development of type 2 diabetes is linked to excess amylin. Pre-diabetic people have elevated amylin levels, which form inflammatory amyloids in the pancreas [48].

Many type 2 patients have clumps (or aggregates) of amylin called amyloid, which interfere with pancreatic cell function. Thus, amylin overproduction may be responsible for the destruction of pancreatic cells in type 2 diabetes patients [49, 50].

Over 90% of type 2 diabetes patients have amyloid deposition in their pancreas [51].

However, after diabetes onset, amylin is deficient in the blood of advanced type 2 diabetes patients [13, 5].

2) Alzheimer’s Disease

Amylin aggregates (clumps of misfolded amylin proteins) can pass through the blood-brain barrier and diffuse into the brain [52].

The aggregates accumulate and cause inflammation. They have also been found together with amyloid B in Alzheimer’s disease patients. Inflammation and amyloid B plaque are key signs of Alzheimer’s disease [53, 54].

People with Alzheimer’s disease, with or without diabetes, have amylin deposits in their brain blood vessels and nerve cells [53].

However, in a mouse model of Alzheimer’s, treatment with low amylin levels helped with Alzheimer’s disease development. Both amylin and its drug version (pramlintide) reduced Alzheimer’s disease markers, including amyloid plaques and brain inflammation, and improved learning and memory in mice [55].

Long-term injection of pramlintide had beneficial effects against Alzheimer’s in mice. However, this may be due to the fact that pramlintide does not form amyloid plaques and reduced amylin aggregation [56].

There is also initial evidence that elderly patients with Alzheimer’s or mild cognitive impairment have lower blood amylin levels compared to other, healthy seniors [32, 57].

High Amylin

1) Kidney Disease

Amylin is normally flushed with urine. When it does not get excreted, amylin accumulates in the blood. Patients with kidney failure may have high blood amylin levels and more amyloids [8].

Factors that May Decrease Amylin Levels

The most important thing is to work with your doctor to determine what underlying condition is causing your high amylin levels and establish a treatment plan. The additional strategies below are other measures that you may try as an add-on to your treatment regime if you and your doctor determine that they could be appropriate.

Losing Weight

Obesity is associated with amylin resistance. Obese patients have higher amylin levels in their blood compared to lean patients. Weight loss may both decrease amylin resistance and lower its resting level [58].

The production of amylin is decreased in obese mice and normalized by leptin [4].

Factors that May Increase Amylin Levels

Again, the most important thing is to work with your doctor to determine what underlying condition is causing your low amylin levels and properly treat it. The following complementary strategies may also work as an add-on to your treatment regime if your doctor determines that they could be helpful in your case.

Natural Methods

Although there aren’t any ways to increase amylin naturally, preliminary evidence suggests some compounds decrease amylin clumping (aggregates) and increase the amount of free amylin in the blood.

In human cells, zinc decreased amylin clumping and inhibited plaque formation [59].

Oleuropein, a component of olive oil, also reduced amyloid formation in human cells [60].

Pramlintide (Symlin)

Pramlintide, a soluble version (analog) of amylin, is approved by the US FDA for diabetes. Given as an injection before mealtime, it helps lower blood sugar if the target level is not achieved with insulin treatment alone. Additionally, unlike amylin, it does not clump together (aggregate) [13].

Health Effects

Effective

Blood Sugar Control in Diabetes

Two 52-week clinical trials on 538 type 2 and 480 type 1 diabetes patients showed that pramlintide further reduced glucose levels compared to insulin treatment alone [61, 62].

In 2 clinical trials on 18 type 1 and 19 type 2 diabetes patients, pramlintide reduced oxidative stress markers (nitrotyrosine, ox-LDL, and TRAP). Oxidative stress causes tissue damage and happens when blood sugar is high (hyperglycemia) [63, 64].

In 2 other trials on 211 type 2 and 187 type 1 diabetes patients, pramlintide reduced a marker of chronic inflammation and heart disease risk: CRP (C-reactive protein). Heart disease risk is higher among diabetes patients compared to healthy people [65, 13].

Possibly Effective

Weight Loss

In a review of a clinical trial involving 930 type 2 diabetes patients and 686 obese people, pramlintide caused mild weight loss in those who were overweight, whether they had diabetes or not [66, 67].

Similarly, pramlintide administration alone resulted in weight loss in another trial on 204 obese people [68].

Additionally, in a trial on 166 obese/overweight people, pramlintide enhanced the weight-loss effects of metreleptin, a version of leptin. Weight loss from the combined treatment was higher than from pramlintide or metreleptin alone [69].

Although the evidence suggests that pramlintide may help with weight loss, it’s not approved for this purpose and other strategies such as doing more exercise and improving your diet may be safer and more effective. You may use pramlintide as an add-on to your weight-loss plan if your doctor determines that it may help in your case.

Animal and Cell Research (Lack of Evidence)

No clinical evidence supports the use of pramlintide for the following condition. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies should not be interpreted as supportive of any health benefit.

Alzheimer’s Disease

Long-term use of its drug version pramlintide had beneficial effects against Alzheimer’s in mice. However, this may be due to the fact that pramlintide does not form amyloid plaques. Pramlintide also reduced amylin aggregation in their brains [56].

Dosage

In clinical trials, type 1 diabetes patients usually started with 15 micrograms of pramlintide and gradually moved up to 30, 45, and 60 micrograms [13].

Type 2 diabetes patients started with 60 micrograms pramlintide and then increased to 120 micrograms after 3 to 7 days.

Note, however, that administering amylin replacement to complement insulin treatments results in a higher risk of insulin-induced hypoglycemia (low blood sugar) in diabetics. When pramlintide is used, the insulin dosage must be reduced by 50% [13].

Carefully follow your doctor’s recommendations and never discontinue the medication or change the dose without consulting it with them beforehand.

Davalintide

Davalintide (AC2307) is a more recently-discovered peptide that mimics amylin’s actions. Not much information is available on this drug [70].

In a study in diet-induced obese rats and healthy mice, davalintide worked longer and was more effective than amylin without further side effects. It suppressed food intake and increased long-term fat loss better than amylin [70].

Genetics of Amylin

Only one type of polymorphism in the human amylin IAPP gene has been found in small Chinese and Japanese populations. It forms amyloids more easily than normal amylin and is associated with a higher incidence of early-onset type 2 diabetes [71].

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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