Open Close
General Information
Name
diabetes mellitus type 2, susceptibility to, IRS1,2-related
FlyBase ID
FBhh0000171
OMIM
Overview

This report describes diabetes mellitus, noninsulin-dependent, IRS1,2-related. The human genes implicated in these forms of noninsulin-dependent diabetes mellitus are IRS1 and IRS2, which are related insulin receptor kinases. There is one fly gene, Dmel\chico, which is orthologous to both human genes, for which classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Neither human gene has been introduced into flies.

Animals that are homozygous for amorphic alleles of Dmel\chico survive to adulthood, but are abnormally small, with lower body weight, fewer ommatidia, smaller wings and fewer cells per wing than wild type; lipid content is increased relative to controls. Physical interactions of the chico protein product have been described; see below and in the FlyBase gene report for chico.

[updated Feb. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: diabetes mellitus, noninsulin-dependent (type 2) (fly models overview)
Symptoms and phenotype

Diabetes mellitus, type 2, also called non-insulin-dependent diabetes mellitus, occurs when cells become resistant to the effects of insulin, thus disrupting the body's ability to metabolize glucose and to properly control the amount of sugar in the blood. [from Genetics Home Reference, Diabetes; 2016.02.02]

Over time, high blood glucose can lead to serious problems such as cataracts and/or retinopathy, impaired kidney function, diabetic neuropathy, and macrovascular complications (heart attack, stroke, peripheral vascular disease). [from endocrineweb; http://www.endocrineweb.com/conditions/type-2-diabetes/type-2-diabetes-complications]

Specific Disease Summary: diabetes mellitus type 2, susceptibility to, IRS1,2-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

See general description, above.

Genetics

The insulin receptor substrate genes IRS1 and IRS2 have been implicated in the development of or susceptibility to diabetes mellitus type 2. [from OMIM:125853; 2016.02.04]

Cellular phenotype and pathology
Molecular information

IRS1 and IRS2 encode proteins which are phosphorylated by insulin receptor tyrosine kinase and thus may mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor, IRS1 protein binds specifically to various cellular proteins containing SH2 domains. [from UniProt:P35568, UniProt:Q9Y4H2; 2016.02.04]

External links
Disease synonyms
diabetes mellitus, noninsulin-dependent, IRS1,2-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; additional orthologous gene in human is IRS1.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila; additional orthologous gene in human is IRS2.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      chico (chico) encodes a substrate of the product of InR. As a key component of the Insulin pathway, the chico product plays an essential role in the control of cell size and growth. [Date last reviewed: 2019-06-13]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human genes IRS1 and IRS2 (1 Drosophila to 2 human). Dmel\chico shares 22-23% identity and 35-37% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (28 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry, fluorescent resonance energy transfer
      experimental knowledge based
      fluorescent resonance energy transfer, anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      experimental knowledge based
      experimental knowledge based
      Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)
      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
      Selected mammalian 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
      amorphic allele - molecular evidence
      P-element activity
      amorphic allele - molecular evidence
      P-element activity
      References (10)