IAPP (amylin): a gut-brain axis hormone involved in metabolic regulation
The islet amyloid polypeptide (IAPP), also known as amylin, is an anorexic neuroendocrine hormone co-secreted with insulin. This molecule has been shown to be deficient in individuals with diabetes and to play an important role in glucose homeostasis.
Interested in measuring IAPP?
Researchers studying diabetes, obesity, cardiometabolic disease and gut-brain signaling can measure circulating IAPP using the Mercodia IAPP ELISA.
What is IAPP (amylin)?
IAPP is a neuroendocrine hormone encoded by chromosome 12 in human. This molecule is produced and stored in pancreatic β-cells together with insulin. IAPP is co-secreted with insulin by the β-cells of the pancreas in response to nutrient stimuli such as glucose, arginine and fatty acids, and plays a major role in regulating blood glucose levels, food intake and body mass.
IAPP synthesis and excretion from the pancreas are similar to insulin, with low levels during fasting and increased levels after a meal. It has been described that the insulin-to-IAPP co-secretion ratio is consistently maintained at approximately 10:1 to 100:1. The circulating half-life of endogenous IAPP is short and has been described as <20 min.
While predominantly produced and secreted by the pancreas, IAPP is also synthesized in lower quantities within other cell types and tissues, including:
- Specific brain regions
- Enteroendocrine cells in the gastrointestinal tract
- Pulmonary tissue
- The central nervous system (CNS)
Learn more about IAPP
Explore the biological functions of IAPP, its relationship with insulin secretion and its emerging role in appetite regulation and metabolic health.
Key facts about IAPP
Alternative name
Amylin
Main source
Pancreatic β-cells
Co-secreted with
Insulin
Mature hormone
37 amino acids (~4 kDa)
Circulating half-life
<20 min
Main physiological functions
Regulation of glucose homeostasis, satiety and gastric emptying
Biosynthesis of IAPP
This 37-residue-long hormone (~4 kDa) is derived from an 89 residue pre-pro-IAPP protein, processed into a 67 residue pro-IAPP, and subsequently into a mature biologically active 37 amino acid protein monomer through cleavage by prohormone convertase 1/3 (PC1/3), prohormone convertase 2 (PC2), and carboxypeptidase-E.
IAPP receptor signaling
Once the mature hormone is secreted it interacts with receptors, with the three most important variants of amylin receptors determined by the type of receptor activity-modifying protein (RAMP), resulting in AMY₁, AMY₂ and AMY₃ receptors (3).
Physiological functions of IAPP
IAPP is known to influence satiation, inhibit glucagon secretion after meals (postprandial secretion), slow gastric emptying and reduce digestive enzyme secretion via both peripheral and central mechanisms.
Regulation of glucose homeostasis
IAPP suppresses postprandial glucagon secretion indirectly and directly through its effects on pancreatic α-cells and reduces hepatic glucose mobilization after nutrient ingestion.
Gastric and digestive regulation
IAPP slows gastric emptying and pancreatic enzyme secretion, lowering glucose levels in the circulation following food intake.
Satiety and food intake
Muhammad et al. refer to the concept of “homeostatic eating control”, where adiposity signals are related to long-term body fat regulation and meal-associated signals respond to food intake.
Studies have also shown that IAPP may improve leptin sensitivity in obesity. Leptin, a hormone secreted by adipose tissue, signals the level of triglycerides in adipose tissue and often becomes less effective in obesity.
Central nervous system effects
IAPP directly targets different structures in the central nervous system through activation of noradrenergic neurons.
Organ-specific actions of IAPP
Beyond its established physiological functions, IAPP has been implicated in a broader range of biological activities. These include:
- Modulation of lipid metabolism through potential effects on chylomicron uptake
- Opposing glycogen synthesis
- Activating glycogenolysis
- Activating glycolysis
- Involvement in neurocognition
- Blood pressure regulation
- Impairment of endothelium-dependent relaxation responses suggesting IAPP-induced hypertension
- Modulation of bone remodelling and formation in animal models
Modified from: Volčanšek et al., Diabetes Therapy, 2025.
IAPP in metabolic and neurological disorders
The physiological actions of IAPP have been implicated in multiple disorders.
Metabolic disorders
- Obesity
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus
- Gestational diabetes
Neurological disorders
- Alzheimer’s disease
- Parkinson’s disease
- Cerebrovascular dementia
- Depression
- Alcohol use disorder
Other associated disorders
- Bone metabolism disorders
- Polycystic ovary syndrome
- Cardiac dysfunction
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Explore the biological functions of IAPP, its relationship with insulin secretion and its emerging role in appetite regulation and metabolic health.
References
1. Amylin: From Mode of Action to Future Clinical Potential in Diabetes and Obesity. Volčanšek, Š., Koceva, A., Jensterle, M., Janež, A., & Muzurović, E. s.l. : Diabetes therapy : research, treatment and education of diabetes and related disorders, 2025, Vols. 16(6), 1207–1227.
2. The role of amylin, a gut-brain axis hormone, in metabolic and neurological disorders. Muhammad, T., Pastore, S. F., Good, K., Yu, W. H., & Vincent, J. B. s.l. : FASEB bioAdvances, 2025, Vols. 7(3), e1480.
3. Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity. Eržen, S., Tonin, G., Jurišić Eržen, D., & Klen, J. s.l. : International journal of molecular sciences, 2024, Vols. 25(3), 1517.
4. Transition State Conformations for IDPs: Application to Human Amylin (hIAPP). Carton, N. A., & Buchete, N. V. s.l. : The journal of physical chemistry. B, 2025, Vols. 129(42), 10998–11005.
5. Amylin Revisited: A 5-Year Perspective on Its Emerging Role in the Treatment of Diabesity. Chung, C. W., & Kim, J. s.l. : Journal of obesity & metabolic syndrome, 2026, Vols. 35(1), 38–48.
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