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Diabetes is commonly associated with insulin. Amylin is another key hormone that helps control blood sugar. It is linked to diabetes, Alzheimer’s, osteoporosis and kidney disease. Read on to find out more about this hormone, and why amylin-mimicking drugs can be useful in 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.
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 [R, R].
Besides controlling blood sugar, amylin may also play important roles in controlling energy usage, blood pressure, and bone metabolism.
Normal Amylin Levels
In a study of 79 subjects, healthy patients have a normal blood amylin level of 6.95 pmol/L (range of 4.45-9.45 pmol/L) [R].
Individuals with obesity, high blood pressure, and 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) [R]
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 activities modifying proteins (RAMPs) [R].
1) Amylin Slows Down Digestion
Amylin in the brain signals to the stomach to slow food movement into the small intestine (gastric/stomach emptying), which helps make you feel full [R].
Also, when carbohydrates stay in the stomach longer, they get broken down to glucose and get absorbed more slowly and gradually.
Diabetes patients have a faster rate of stomach emptying and glucose absorption due to a lack of amylin [R].
2) Amylin Blocks Glucagon
In rats, blocking amylin function resulted in higher glucagon levels [R].
3) Amylin Makes You Feel Full (Helps In Weight Loss)
You stop eating when you feel “full”.
Amylin acts as a satiation factor (inducing a feeling of “fullness”) after food intake by activating amylin/calcitonin receptors in the brain [R].
Rats ate less food when injected with amylin within a few minutes [R].
Also, blocking amylin in the area postrema increases food intake in rats [R].
Finally, amylin also reduced food-related motivated behaviors in animals, suggesting that, apart from causing a feeling of fullness, it also reduces the rewarding effects of food [R].
4) Amylin Increases Sensitivity to Leptin
Amylin increases sensitivity to leptin. Leptin is a hormone produced by fat cells and it stimulates fat burning but inhibits hunger. Many obese individuals are leptin resistant although they have high leptin levels from having more fat cells [R].
In a study (DB-RCT) of 177 obese/overweight subjects, metreleptin administration (an analog/version of leptin) alone did not result in weight loss. However, administering it with Pramlintide (an amylin drug) resulted in significant weight loss [R].
5) Amylin Helps Control Energy Expenditure And Body Weight
In various animal studies, long-term amylin administration decreased body weight and fat gain, while stopping amylin activity increased body fat. Therefore, amylin can contribute to the balance of body weight [R, R].
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) have reduced body weight and fat mass increased energy expenditure and body temperature [R, R, R].
6) Amylin And Blood Pressure
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 [R, R].
7) Amylin Helps 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 [R].
In diabetic mice, amylin exerted bone remodeling effects and helped with bone growth [R].
In mice, inactivating amylin led to low bone mass [R].
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 [R].
8) Amylin May Improve Cognitive Function
9) Amylin May Have Some Antipsychotic Effects
Amylin injections in certain parts of the rat brain (accumbens shell) reduced psychotic behavior. Thus, amylin receptors may be a potential target for antipsychotic drug development [R].
1) Amylin Aggregates And Forms Plaques
Amylin can self-aggregate (combine together) and eventually form amyloid plaques [R].
High amylin levels contribute to the early processes of amyloid formation in the brain and spinal cord. Meanwhile, low amylin levels are more strongly associated with the late stages of amyloid disorders [R].
Amyloids are hard to study because unlike in humans, the amylin in rats does not form plaques [R].
Diseases Linked to Amylin
1) Low Amylin Is Linked to Type I Diabetes
Amylin production is lower or nonexistent in the pancreas of type 1 diabetes patients [R].
2) Both High And Low Amylin Are Linked to 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 [R].
Development of type 2 diabetes is linked to excess amylin. Pre-diabetes patients have elevated amylin levels, which form inflammatory amyloids in the pancreas [R].
Many type 2 patients have clumps (or aggregates) of amylin called amyloid, which interfere with pancreas cell function. Thus, amylin overproduction may be responsible for the destruction of pancreas cells in type 2 diabetes patients [R, R].
Over 90% of type 2 diabetes patients have amylin amyloid deposition in their pancreas [R].
3) Both Low and High Amylin May Contribute to Alzheimer’s Disease
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 the telling signs seen in Alzheimer’s patients [R, R].
Patients with Alzheimer’s disease, with or without diabetes, have amylin deposits in their brain blood vessels and nerve cells [R].
However, in a mouse model of Alzheimer’s, low amylin levels helped with Alzheimer’s disease development. Recent mice studies showed that treatments with amylin or its drug version (pramlintide) reduced Alzheimer’s disease markers, including amyloid plaques and brain inflammation. This corresponded with improved learning and memory in the mice [R].
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 and reduced amylin aggregation in the mice [R].
4) High Amylin Is Linked to Kidney Disease
Amylin is normally excreted in the urine. When it does not get excreted, amylin accumulates in the blood. Patients with kidney (renal) failure may have high blood amylin levels and more amyloids [R].
5) Low Amylin Is Linked to Reduced Bone Strength/Osteoporosis
Amylin is a member of the calcitonin family of hormones and can affect bone formation. Amylin stimulates the spread of cells that help with bone formation and absorption [R].
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 (cross-sectional) of 31 healthy women and women with anorexia [R].
In a study of 52 healthy, diabetic, and osteoporosis patients, the osteoporosis patients had lower amylin levels. These low levels may contribute to osteoporosis development [R].
Amylin-deficient mice also have lower bone mass [R].
Bone loss observed in type 1 diabetes patients has been associated with amylin deficiency [R].
Ways to Decrease Amylin Levels
Losing Weight Helps Decrease Amylin
Obesity is linked with amylin resistance. Obese patients have higher amylin levels in their blood compared to lean patients. Weight loss could decrease amylin resistance and lower its resting level [R].
The production of amylin is decreased in obese mice and normalized by leptin[R].
Ways to Increase Amylin Levels
Although there aren’t any ways to increase amylin naturally, you can decrease amylin clumping (aggregates) and increase the amount of free amylin in the blood.
Pramlintide, a soluble version (analog) of amylin, is approved by the US FDA for diabetes. Given in the form of injection before mealtime, it helps lower blood sugar, if target blood sugar level is not achieved with insulin treatment alone. Additionally, unlike amylin, it does not clump together (aggregate) [R].
Pramlintide Helps Control Blood Sugar in Diabetes
In two studies (both RCT), with 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) [R, R].
In two studies (DB-RCT) of 211 type 2 and 187 type 1 diabetes patients, pramlintide reduced a chronic inflammation and heart disease risk marker, CRP (C-reactive protein). Heart disease risk is higher among diabetes patients compared to healthy subjects [R, R].
Pramlintide Can Improve Weight Loss
In a study (DB-RCT) of 204 obese subjects, pramlintide administration alone resulted in weight loss [R].
Additionally, in a study (DB-RCT) of 166 obese/overweight subject, pramlintide increased weight loss when administered with metreleptin, a version of leptin. Weight loss from amylin and metreleptin treatment was higher than from pramlintide or metreleptin treatment alone [R].
Pramlintide May Help in Alzheimer’s Disease
Long-term use of its drug version pramlintide had beneficial effects against Alzheimer’s. However, this may be due to the fact that pramlintide does not form amyloid plaques. Pramlintide also reduced amylin aggregation in their brains [R].
In various studies, Type 1 diabetes patients usually start with 15 micrograms of pramlintide and gradually move up to 30, 45, and 60 micrograms [R].
Type 2 diabetes patients start with 60 micrograms pramlintide and then increase to 120 micrograms after 3 to 7 days.
Administering and amylin replacement to complement insulin treatment results in higher risk of insulin-induced hypoglycemia (low blood sugar) in diabetics. When pramlintide is used, a dosage of insulin is reduced by 50% [R].
Davalintide (AC2307) is a newly discovered peptide that mimics amylin’s actions. Not much information is available on davalintide [R].
In a study (RCT) with 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 [R].
Amylin and Genes
Only one type of mutation in the human amylin IAPP gene has been found, in a small part of the Chinese and Japanese population. It forms amyloids more easily than normal amylin and is linked with a higher risk of early-onset type 2 diabetes [R].
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