FB2026_03 , released September 17, 2026
Human Disease Model Report: insulin pathway effects, IDE-related
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General Information
Name
insulin pathway effects, IDE-related
FlyBase ID
FBhh0001171
Disease Ontology Term
Parent Disease
OMIM
Overview

In genome-wide association studies (GWAS), the human gene IDE has been associated with type 2 diabetes and waist-to-hip ratio. Deficiencies in IDE protein function are associated with Alzheimer disease and type 2 diabetes mellitus, but specific mutations in the IDE gene have not been shown to be causative for either disease. IDE encodes a zinc metallopeptidase that degrades intracellular insulin, as well as a diverse collection of other peptides. There is a single orthologous gene in Drosophila, Dmel\Ide, for which an amorphic allele created by targeted recombination, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Several different UAS constructs of the wild-type human Hsap\IDE gene have been introduced into flies and have been characterized in terms of impact on the fly insulin signaling pathway.

Results in flies suggest a conserved role for IDE in sugar metabolism. Animals homozygous for an amorphic mutation of Dmel\Ide are viable and fertile, however, they display a higher level of the sugar trehalose in their hemolymph. Circulating levels of trehalose drop sharply after 24 hr starvation in wild type adult flies; in Ide mutant animals levels remain close to those observed before starvation. An increased developmental delay is observed when larvae are raised on a high-sucrose diet. A small number of physical and genetic interactions have been described for Dmel\Ide; see below and in the Ide gene report.

[updated Jan. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: insulin pathway effects, IDE-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

IDE is associated with type 2 diabetes and waist-to-hip ratio in GWAS studies (see GWAS Catalog, below in 'External links').

Deficiencies in IDE protein function are associated with Alzheimer disease and type 2 diabetes mellitus, but mutations in the IDE gene have not been shown to be causative for these diseases. [Gene Cards, IDE; 2020.01.24]

Cellular phenotype and pathology
Molecular information

IDE encodes a zinc metallopeptidase that degrades intracellular insulin, as well as participating in intercellular peptide signalling by degrading diverse peptides such as glucagon, amylin, bradykinin, and kallidin. It may play a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia. [Gene Cards, IDE; 2020.01.24]

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Insulin degrading metalloproteinase (Ide) encodes a metalloprotease that controls growth in a cell-autonomous manner by regulating the level of the insulin-like peptide encoded by Ilp2. [Date last reviewed: 2018-09-13]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human IDE (1 Drosophila to 1 human).

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (2 groups)
      protein-protein
      Interacting group
      Assay
      References
      proximity-dependent biotin identification, Identification by mass spectrometry
      RNA-protein
      Interacting group
      Assay
      References
      anti bait coimmunoprecipitation, quantitative reverse transcription pcr
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 3 )
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      References (6)