Amylin's Role in Obesity and Alzheimer's

Increase Your Metabolism While Decreasing Food Intake

Amylin plays a role in enhancing the metabolism, fighting cognitive diseases, obesity and inflammation. 



Amylin is a hormone that is co-stored and co-secreted with insulin from the pancreatic beta cells in response to nutrients (eating). R

It mediates important brain functions, including appetite inhibition, cerebrovascular structure relaxation, and neural regeneration. R

It also plays a role in regulating glucose metabolism and modulating inflammation. R

Amylin shares characteristics of satiation signals, like CCK, but also of adiposity signals, like leptin or insulin. R

Amylin plays a role in:

  • Alzheimer's Disease and Dementia R
  • Anorexia R
  • Obesity R
  • Osteoporosis R
  • Type 1 Diabetes (can be a biomarker of pancreatic problems) R
  • Type 2 Diabetes R

It is also called islet amyloid polypeptide (IAPP). R

Energy And Metabolism


Amylin increases energy expenditure. R R

It can do this independently of food intake. R

It modulates insulin secretion, glycogen synthesis and glucose uptake. R 

Amylin exerts dual effects on the blood pressure by stimulating renal release of renin and relaxation of blood vessels. R

Hypersecretion of amylin, (hyperamylinemia) may increase hyperinsulinemia.R

It is common in individuals with obesity or pre-diabetic insulin resistance. R

Hyperamylinemia may accelerate the development of diabetic heart disease and trigger arrhythmia in an animal model of myocardial amylin accumulation. R

Amylin also increases lipid metabolism and may raise body temperature.  


Amylin is able to reduce eating (within minutes). R

It does this by promoting a satiety effect, which you normally get after eating a meal. R

It also controls gastric acid secretion and how fast the stomach empties. R

Amylin is high in obese patients, which may mean the brain isn't reacting to signals of amylin. R

This is probably from "amylin resistance" or decreased amylin sensitivity. R

It may be caused by damage to the AP. R

This creates a positive feedback loop: eating more, creating more amylin, the brain not identifying that amylin is being secreted, and you wanted to eat more. 

Direct administration to the brain of amylin would temporarily fix this problem.

For example, when rats were injected with amylin into the hypothalamus, they displayed anorexic behaviors and did not want to eat. R

Also, when amylin is chronically administered into the rat's brains, they lost weight and fat. R

Taking an amylin receptor antagonist (or blocker) made them gain weight again. R

Rats genetically made to not produce amylin are significantly heavier. R

Anti-histamines will block amylin's ability to reduce eating. R

CCK And Leptin


Amylin is different than CCK, since continuous CCK infusion doesn't result in sustained food reduction or body weight decrease. R

Also, CCK may increase the frequency of meals, while decreasing meal size, whereas amylin doesn't. R

Amylin enhances the effects of leptin. R

Also, leptin can increase the inhibitory effects on eating created by amylin. R

For example, obese rats that were only given leptin has no change in weight loss, but when combined with amylin, they saw significant weight loss (2x as much as amylin alone). R

There was more energy expenditure with the combo of both amylin and leptin. R

Amylin is able to increase leptin sensitivity, which beneficial for leptin resistance. R

Amylin can also enhance Neuropeptide Y and alpha-MSH's pathways. R

Organ-Mediated Effects

Amylin influences the development of the kidneys, of bone, and of the pancreas. R

It inhibits bone resorbtion and helps increase bone mass density. R

For example, mice that were deficient in amylin display symptoms similar to osteoporosis. R

Amylin inhibits osteoclastogenesis (which grows bone cells that breaks down bone tissue). R

It also helps muscle cells release free glucose and excess lactate, enhancing muscle contractibility. R

Amylin can also modulate pain. R R

Alzheimer's, Inflammation, And Immunity


Elderly patients that are cognitively impaired can have high levels of fasting amylin. R

Type II diabetes (T2D), Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntingdon’s disease (HD) are associated with protein and amyloid formations. R

The primary components of amyloid and fibril-forming molecules are called hIAPP (amylin and insulin). R

In the brain, amylin can cause neuroinflammation, . R

Patients with T2D and dementia or AD contains significant accumulation amylin in the brain and amyloid plaques contain more than 95% amylin. R R

This correlates how the majority of patients with T2D have abundant amylin amyloid deposition in the pancreas.  R

Hyperamylinemia (excess excretion of amylin) can cause amylin to store in the brain. R

High levels of amylin in the brain are associated with pro-inflammatory markers such as TNF-a and IL-6, while anti-inflammatory markers like IL-10 are decreased. R

Amylin activates microglia to stay in a M1 state. R

Small amyloid plaques (mediated by TRPV4) can infiltrate cellular membranes leading to Ca2+ dysregulation (forming ion channels on lipid bilayers and disrupting ionic homeostasis), oxidative stress, inflammation, and cell death. R R R

Amylin makes it easier for amyloid-beta to cross the blood brain barrier. R

Both Aβ and amylin accumulation can be a response of the innate immune system to invading pathogens. R

This is because amylin can act as an antimicobial. R

Interestingly, when exogenous amylin was given to mice, neuroinflammation went down, helping deactivating microglia inflammation and LPS induced inflammation (via Cd68 and Atp5b). R

Injecting amylin into organ tissue reduces β-amyloid (Aβ) peptide from the brain. R

Mechanism Of Action


Amylin is a 37 amino acid peptide of the CGRP family excreted from the pancreas (pancreatic beta-cells) along with insulin. R

For satiety, amylin reacts with its receptors (CGRP and AMY1) in the area postrema (AP). R

This signals to the forebrain then to the nucleus of the solitary tract (NTS), the lateral parabrachial nucleus (lPBN), the lateral hypothalamic area (LHA) and other hypothalamic nuclei. R R

Amylin receptors are also found in the arteries. R

Amylin also binds to calcitonin core receptor (CT-R), together with several receptoractivity modifying proteins (RAMPs) that confer amylin affinity and selectivity. R

The amylin-leptin interaction happens in the hypothalamus (specifially the VMH and DMN). R


  • Anorexigenic (suppresses appetite) R
  • Increases Cyclic guanosine monophosphate (cGMP) formation R
  • Increases cAMP R
  • Increases DOPAC (dopamine metabolite), tryptophan, and 5-HIAA, but may decrease phenylalanine. R R
  • Increases IL-6 (mediating the leptin-sensitizing effects of amylin) R
  • Increases leptin receptor expression in the DMN and binding in the VMN R R
  • Increases pERK formation R
  • Increases pSTAT3 formation R
  • Induces neurogenesis in the Area Postrema (effecting Ephrin and GABA genes and satiety) - may be causing amylin resistance? R
  • Reduces H2O2 by Cu2+ and glutathione R
  • Switches microglia into M1 pro-inflammatory state R
  • Transports well across the blood-brain barrier R

How To Increase Or Decrease Amylin

Hyperamylinea is bad for cognitive disorders and low amylin for bone density and obesity. So keeping a happy medium is probably best.




Amylin blocks the benefits of fasting. R

Also if amylin is too low, you may not be able to gain a certain amount of weight. R

More Research

  • Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin. R