Human Disease Model Report: pancreatic islet amyloidosis, IAPP-related

General Information

Name

pancreatic islet amyloidosis, IAPP-related

FlyBase ID

FBhh0000351

Disease Ontology Term

amyloidosis

Parent Disease

OMIM

Overview

Islet amyloid polypeptide (IAPP or amylin) plays a role in the maintenance of energy homeostasis and glucose utilization. It is normally produced as a prohormone in pancreatic beta cells and processed by proprotein convertases. IAPP is highly amyloidogenic; aggregated IAPP is cytotoxic and is believed to be of critical importance for the loss of β-cells in type 2 diabetes. Deficiency in processing of proIAPP into IAPP is associated with an increase in amyloidogenicity. There is no gene orthologous to IAPP in Drosophila.

UAS constructs of Hsap\IAPP, both the processed form and the prohormone form, have been introduced in flies. Since it has been shown previously that the mouse IAPP protein does not exhibit the amyloidogenic properties observed for the human protein, for comparison Mmus\Iapp has also introduced into flies. Using a pan-neuronal GAL4 driver, flies expressing proIAPP (but not IAPP) exhibit a reduction in lifespan; both IAPP and proIAPP expression cause formation of amyloid aggregates in head fat body, as well as in neurons of the CNS. Neither of these phenotypes is observed upon pan-neuronal expression of the mouse IAPP gene.

[updated Aug. 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: pancreatic islet amyloidosis, IAPP-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Aggregated IAPP has cytotoxic properties and is believed to be of critical importance for the loss of β-cells in type 2 diabetes (Westermark et al., 2011; pubmed:21742788).

(FlyBase Curators, 2013-)

Amyloid is commonly found in the pancreatic islets (islets of Langerhans) of patients with diabetes mellitus type II and in insulinomas. [from MIM:147940; 2016.07.29]

(OMIM, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

Islet amyloid polypeptide (IAPP) is produced by the pancreatic beta cells as a prohormone (proIAPP); proIAPP is processed into IAPP in the secretory granules. Both proIAPP and IAPP spontaneously form amyloid-like fibrils in vitro. [references cited in FBrf0214011]

(FlyBase Curators, 2013-)

Islet amyloid polypeptide (IAPP) is a 37-amino acid monomeric polypeptide originally isolated from pancreatic amyloid; it is derived from an 89-amino-acid precursor by proteolytic processing. A specific immunoreactivity with antibodies to IAPP is found in islet amyloid and in cells of the islets of Langerhans, where it colocalizes with insulin in islet B cells. [from MIM:147940; 2016.07.29]

(OMIM, 2013-)

External links