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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IAPP
islet amyloid polypeptide
Chromosome 12 · 12p12.1
NCBI Gene: 3375Ensembl: ENSG00000121351.9HGNC: HGNC:5329UniProt: P10997
357PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
identical protein bindingpositive regulation of calcium-mediated signalingamylin receptor 3 signaling pathwayamylin receptor signaling pathwayAL amyloidosisAlzheimer diseasediabetes mellituscancer
✦AI Summary

IAPP (islet amyloid polypeptide), also known as amylin, is a glucoregulatory peptide hormone critical for energy homeostasis. It selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle through amylin receptor (AMYR) complexes while leaving adipocyte glucose metabolism unaffected 1. IAPP plays a metabolic role in postprandial glucose regulation by delaying gastric emptying and suppressing hyperglucagonemia 2. In type 2 diabetes, pathological IAPP accumulation becomes problematic. Human IAPP forms cytotoxic oligomers and amyloid fibrils in pancreatic islets, with toxicity primarily associated with early-phase oligomeric intermediates rather than mature fibrils 3. Both intracellular misfolding—triggered by protein synthesis defects, unfolded protein response failure, or degradation pathway overload—and extracellular amyloid-membrane interactions drive β-cell apoptosis 3, 4. Metabolic stress from insulin resistance and hyperglycemia exacerbates IAPP production and aggregation propensity 4. IAPP also functions as an islet autoantigen in type 1 diabetes, with autoreactive T cells targeting IAPP-derived epitopes, and IAPP aggregates act as pro-inflammatory stimuli 2. The peptide's therapeutic potential has been explored through IAPP analogues like pramlintide and novel inhibitors including silybins and graphene quantum dots, which prevent aggregation and protect β-cells from toxicity 5, 6.

Sources cited
1
IAPP is a glucoregulatory peptide hormone that plays an important role in the regulation of energy homeostasis and selectively inhibits insulin-stimulated glucose utilization in muscle
PMID: 2690069
2
IAPP forms cytotoxic oligomers and amyloid fibrils in islets in type 2 diabetes, with cytotoxicity associated with early-phase oligomers/multimers; intracellular and extracellular mechanisms both contribute to β-cell apoptosis
PMID: 28811318
3
IAPP amyloid aggregates are toxic to β-cells and induce β-cell death and dysfunction; metabolic stress from insulin resistance and hyperglycemia increases IAPP production and amyloid formation
PMID: 22928566
4
IAPP is an islet autoantigen in type 1 diabetes with autoreactive T cells targeting IAPP-derived epitopes; IAPP aggregates are pro-inflammatory; IAPP analogues like pramlintide limit postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia
PMID: 29378867
5
Silybin compounds inhibit human IAPP aggregation and protect cells from hIAPP toxicity through stereospecific interactions with amyloidogenic regions
PMID: 35307557
6
Graphene quantum dots inhibit human IAPP aggregation and toxicity in vivo through electrostatic, hydrophobic, and hydrogen bonding interactions
PMID: 30350837
Disease Associationsⓘ20
AL amyloidosisOpen Targets
0.46Moderate
Alzheimer diseaseOpen Targets
0.12Weak
diabetes mellitusOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
alcohol drinkingOpen Targets
0.10Suggestive
type 2 diabetes mellitusOpen Targets
0.10Suggestive
MODYOpen Targets
0.09Suggestive
goutOpen Targets
0.09Suggestive
head and neck squamous cell carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
Mobius syndromeOpen Targets
0.09Suggestive
complicationOpen Targets
0.08Suggestive
hemorrhageOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.08Suggestive
Gorham-Stout diseaseOpen Targets
0.08Suggestive
metabolic syndromeOpen Targets
0.08Suggestive
infectionOpen Targets
0.08Suggestive
pulmonary vascular congestionOpen Targets
0.07Suggestive
nail-patella syndromeOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RAMP3Protein interaction100%RAMP1Protein interaction100%RAMP2Protein interaction100%ADMProtein interaction99%CALCBProtein interaction99%CALCRLProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Lung
67%
Ovary
38%
Brain
18%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
IAPPRAMP3RAMP1RAMP2ADMCALCBCALCRL
PROTEIN STRUCTURE
Preparing viewer…
PDB8YG2 · 1.25 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.50LoF Tolerant
pLIⓘ
0.35Tolerant
Observed/Expected LoF0.35 [0.12–1.50]
RankingsWhere IAPP stands among ~20K protein-coding genes
  • #866of 20,598
    Most Researched357 · top 5%
  • #15,166of 17,882
    Most Constrained (LOEUF)1.50
Genes detectedIAPP
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
The β-cell assassin: IAPP cytotoxicity.
PMID: 28811318
J Mol Endocrinol · 2017
1.00
2
Modulating human IAPP aggregation in type 2 diabetes: inhibitors, mechanisms, and translational challenges.
PMID: 41732094
Future Med Chem · 2026
0.96
3
IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants.
PMID: 29378867
J Mol Endocrinol · 2018
0.90
4
Silybins inhibit human IAPP amyloid growth and toxicity through stereospecific interactions.
PMID: 35307557
Biochim Biophys Acta Proteins Proteom · 2022
0.80
5
Differential Effects of Aromatic Residues on Amyloid Formation and Cytotoxicity of Human IAPP.
PMID: 36215164
Biochemistry · 2022
0.72