Human Disease Model Report: diabetes mellitus type 2, susceptibility to, IRS1,2-related

General Information

Name

diabetes mellitus type 2, susceptibility to, IRS1,2-related

FlyBase ID

FBhh0000171

Disease Ontology Term

type 2 diabetes mellitus

Parent Disease

diabetes mellitus, noninsulin-dependent (type 2) (fly models overview)

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]

(FlyBase Curators, 2013-)

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]

(FlyBase Curators, 2013-)

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.

(OMIM, 2013-)

Genetics

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

(OMIM, 2013-)

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]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): IRS1
Gene2Function (human gene): IRS2
Gene Cards: IRS1
Gene Cards: IRS2
MedlinePlus (gene): IRS1
MedlinePlus (gene): IRS2
MARRVEL (human gene): IRS1
MARRVEL (human gene): IRS2
NCBI MedGen: Diabetes mellitus type 2 (NIDDM)
NCBI (Entrez) gene: IRS1; insulin receptor substrate 1
NCBI (Entrez) gene: IRS2; insulin receptor substrate 2

Disease synonyms

diabetes mellitus, noninsulin-dependent, IRS1,2-related

Related Diseases

Related human health report(s)

cancer, epithelial, SCRIB-hyperinsulinemia model

diabetes mellitus, noninsulin-dependent (type 2) (fly models overview)

diabetes mellitus type 2, susceptibility to (postulated), UCHL1-related

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

IRS2; insulin receptor substrate 2

D. melanogaster ortholog (based on DIOPT)

Dmel\chico

(DIOPT, 2013-)

Comments on ortholog(s)

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

Human gene (HGNC)

Symbol / Name

IRS1; insulin receptor substrate 1

D. melanogaster ortholog (based on DIOPT)

Dmel\chico

(DIOPT, 2013-)

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)

Dmel\chico

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]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

INS-C

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

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (28 groups)

chico

protein-protein

Interacting group

Assay

References

chico - 14-3-3ε

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011, Pflieger et al., 2008)

chico - 14-3-3ζ

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011, Pflieger et al., 2008)

chico - CG7668

experimental knowledge based

(Guruharsha et al., 2011)

chico - cmb

experimental knowledge based

(Guruharsha et al., 2011)

chico - dos

experimental knowledge based

(Guruharsha et al., 2011)

chico - Flo1

experimental knowledge based

(Guruharsha et al., 2011)

chico - Flo2

experimental knowledge based

(Guruharsha et al., 2011)

chico - Hsc70-3

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - InR

anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting, two hybrid, fluorescent resonance energy transfer

(Breitkopf et al., 2016, Vinayagam et al., 2016, Almudi et al., 2013, Friedman et al., 2011, Glatter et al., 2011, Pflieger et al., 2008, Kulansky Poltilove et al., 2000)

chico - Ist1

experimental knowledge based

(Guruharsha et al., 2011)

chico - Lnk

fluorescent resonance energy transfer, anti tag coimmunoprecipitation, western blot

(Almudi et al., 2013, Song et al., 2010)

chico - mib2

experimental knowledge based, anti tag coimmunoprecipitation, peptide massfingerprinting

(Glatter et al., 2011, Guruharsha et al., 2011)

chico - Pgam5

anti tag coimmunoprecipitation, peptide massfingerprinting

(Glatter et al., 2011)

chico - Pi3K21B

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011)

chico - Pi3K92E

anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting

(Breitkopf et al., 2016, Vinayagam et al., 2016)

chico - Pp2A-29B

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RanBPM

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL4

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL7A

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL14

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL17

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL18

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL30

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpS15Aa

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpS26

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - tws

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - Vps4

experimental knowledge based

(Guruharsha et al., 2011)

chico - Vps60

experimental knowledge based

(Guruharsha et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

chico

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

chico¹

model of type 2 diabetes mellitus

CEA

(Murillo-Maldonado et al., 2011)

model of intellectual disability

CEA

(Naganos et al., 2016)

model of glucose metabolism disease

CEA

(Naganos et al., 2012)

CEA with chico^flp147E

(Naganos et al., 2012)

model of amnestic disorder

CEA

(Naganos et al., 2012)

CEA with chico^flp147E

(Naganos et al., 2012)

chico^flp147E

model of glucose metabolism disease

CEA with chico¹

(Naganos et al., 2012)

model of amnestic disorder

CEA with chico¹

(Naganos et al., 2012)

chico^HMS01553

model of type 2 diabetes mellitus

CEA

(Tsao et al., 2023)

chico^{lexAop.HMS01553}

model of type 2 diabetes mellitus

CEA

(Tsao et al., 2023)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

chico¹

ameliorates Parkinson's disease

modeled by Hsap\SNCA^UAS.cFa

(Knight et al., 2014)

model of intellectual disability

is ameliorated by Adcy1^UAS.cUa

(Naganos et al., 2016)

exacerbates cancer

modeled by scrib¹

(Sanaki et al., 2020)

chico^KG00032

ameliorates viral infectious disease

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates infectious mononucleosis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates Epstein-Barr virus hepatitis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

chico^KK107581

exacerbates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-GR^50.UAS.EGFP

(Lee et al., 2016)

ameliorates cancer

modeled by Pten^KK109278

(Parniewska and Stocker, 2020)

exacerbates cancer

modeled by scrib¹

(Sanaki et al., 2020)

chico^UAS.cNa

ameliorates type 2 diabetes mellitus

modeled by Uch^KO

(Lee et al., 2024)

chico^UAS.cCa

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Chatterjee et al., 2019)

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

Metabolism/Diabetes/Obesity

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

chico^UAS.cCa

P{UAS-chico.C}

w¹¹¹⁸; P{UAS-chico.C}3/TM3, Sb¹

chico^UAS.cNa

P{UAS-chico.N}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

chico^RNAi.UAS.cUa

P{UAS-chico.RNAi.U}

chico^{lexAop.HMS01553}

P{lexAop-HMS01553}

chico^GD1402

P{GD1402}

w¹¹¹⁸; P{GD1402}v7776

y¹ sc^* v¹ sev²¹; P{TRiP.GL00525}attP40

chico^HMS01553

P{TRiP.HMS01553}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01553}attP2/TM3, Sb¹

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

chico¹

amorphic allele - molecular evidence

P-element activity

cn¹ P{ry11}chico¹/CyO; ry⁵⁰⁶

chico^KG00032

P-element activity

y¹ w^67c23; P{SUPor-P}chico^KG00032

chico^flp147E

amorphic allele - molecular evidence

P-element activity

References (13)

Report Sections

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