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FLASH GENE

Symbol

IAPP

contributors: mct - updated : 12-10-2016

HGNC name	islet amyloid polypeptide
HGNC id	5329

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas       highly Homo sapiens Lymphoid/Immune lymph node       highly Reproductive female system placenta     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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