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FLASH GENE
Symbol IAPP contributors: mct - updated : 12-10-2016
HGNC name islet amyloid polypeptide
HGNC id 5329
Location 12p12.2      Physical location : 21.525.801 - 21.532.913
Synonym name
  • diabetes-associated peptide
  • amylin
  • insulinoma amyloid peptide
    • Synonym symbol(s) AMYL, DAP, IAP
    DNA
    TYPE functioning gene
    STRUCTURE 25.05 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1992 - 89 - 1992 1282806
    - - 1909 - 89 - 1992 1282806
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly Homo sapiens
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemplacenta  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal signal sequence
  • cysteine residues in position 2 and 7
    • HOMOLOGY
    interspecies homolog to murine Iapp
    Homologene
    FAMILY calcitonin family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • selectively inhibiting insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism
  • stored with insulin in beta-islet cells and aggregates in the islet extracellular space to form amyloid deposits in patients with the disease
  • IAPP and SERPINA12 are modulated by energy status in the placenta, which suggests that these proteins may be involved in the regulation of placental metabolic functions (pMID: 19554505)
  • APP and IAPP both exert toxicity, at least in part, via mitochondrial dysfunction, thus restoring their function may be beneficial for both AD and T2DM
  • regulatory peptide with putative function both locally in the islets, where it inhibits insulin and glucagon secretion, and at distant targets
  • its overexpression inhibits insulin and IAPP secretion in response to glucose affecting the activity of KCNJ channels and the increased mitochondrial metabolism is a compensatory response to counteract the secretory defect of beta-cells
  • IAPP plays a role in the maintenance of energy homeostasis by regulating several metabolic parameters, such as satiety, blood glucose levels, adiposity and body weight
  • is a beta cell hormone secreted together with insulin upon glucose stimulation
  • having ability to misfold and form islet amyloid
  • autophagy/lysosomal degradation defends beta cells against proteotoxicity induced by oligomerization-prone human IAPP
  • IAPP aggregation induces processes that impair the functionality and viability of beta-cells and may lead to apoptosis
  • secreted IAPP contributes to the signaling and mitogenic response of beta cells to glucose through an autocrine mechanism
  • is the major component of amyloid deposits in islets of type 2 diabetic patients
  • type 2 diabetes is characterized by a deficit in beta-cell mass as a result of misfolded IAPP which forms toxic aggregates that destroy pancreatic beta-cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
  • zinc binds unaggregated IAPP at micromolar concentrations similar to those found in the extracellular environment, by contrast, the fibrillar amyloid form of IAPP has low affinity for zinc
    • protein
  • MME protected against beta cell cytotoxicity induced by exogenously added or endogenously produced human IAPP
  • MMP9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of IAPP
  • chaperones ameliorate beta cell dysfunction associated with IAPP overexpression
  • cholesterol modulates the interaction of IAPP with membranes
  • MMP9 is active in islets and cleaves IAPP
  • IAPP is also a known substrate of the protease insulin-degrading enzyme (IDE)
    • cell & other
    REGULATION
    Other NUCB1 prevent IAPP fibril formation and disaggregate preexisting IAPP fibrils
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    basal IAPP secretion is higher in T2DM and impaired glucose tolerance versus normal glucose tolerance but is reduced in response to hyperglycemia and arginine
    constitutional     --over  
    in young with new-onset of type 1 diabetes mellitus
    constitutional     --over  
    in women with polycystic ovary syndrome
    Susceptibility for NIDDM12 (in japanese)
    Variant & Polymorphism other mutation S2OG, inducing aggregation in the islet extracellular space to form amyloid deposits
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS