Human Disease Model Report: diabetes mellitus, pathogenic impact, glyoxalase function

General Information

Name

diabetes mellitus, pathogenic impact, glyoxalase function

FlyBase ID

FBhh0000993

Disease Ontology Term

type 2 diabetes mellitus

Parent Disease

OMIM

Overview

Diabetes patients frequently have elevated levels of the toxic metabolite methylglyoxal. The glyoxalase enzymatic pathway is involved in the detoxification of methylglyoxal and similar compounds; the glyoxalase I gene (GLO1), is a key enzyme in that pathway. There is a single gene orthologous to GLO1 in Drosophila, which shares the symbol Glo1. RNAi targeting constructs, alleles caused by insertional mutagenesis, and an amorphic mutation caused by imprecise excision of a TE insertion have been generated for Dmel\Glo1.

The human GLO1 gene has not been introduced into flies.

Animals homozygous for an amorphic mutation Dmel\Glo1 are viable, despite elevated levels of methylglyoxal; in fact, they have an increased lifespan. They exhibit phenotypes that recapitulate several core aspects of type 2 diabetes: insulin-resistance by larval stages, progressive obesity in the adult stage, and hyperglycemia beginning in mid to late adult stage. It is postulated that in terms of of causality, elevated levels of methylglyoxal may be upstream of insulin resistance and hyperglycemia, as well as downstream, generating an intensifying pathogenic cycle.

[updated Mar. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: diabetes mellitus, pathogenic impact, glyoxalase function

OMIM report

Human gene(s) implicated

Symptoms and phenotype

High plasma methylglyoxal levels are associated with higher risk of development of cardiovascular disease in both diabetes type I and type II patients (Hanssen et al., 2017, pubmed:28588100; Hanssen, et al., 2018, pubmed:29784769).

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

Methylglyoxal is the major precursor of advanced glycation endproducts (AGEs); formation and accumulation of AGEs are related to diabetes and other age-related diseases (Maessen et al., 2015: pubmed:25818485).

(FlyBase Curators, 2013-)

The GLO1 gene encodes glyoxalase I. The glyoxalase enzymatic pathway is involved in the detoxification of methylglyoxal and the other reactive aldehydes which are produced as cytotoxic byproducts of glycolysis and other normal metabolic pathways.

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): GLO1
Gene Cards: GLO1
MedlinePlus (gene): GLO1
MARRVEL (human gene): GLO1
NCBI (Entrez) gene: GLO1; glyoxalase I

Disease synonyms

Related Diseases

Related human health report(s)

diabetes mellitus, insulin-dependent (type 1) (fly models overview)

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

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

GLO1; glyoxalase I

D. melanogaster ortholog (based on DIOPT)

Dmel\Glo1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Glo1

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

cytosol

Gene Groups / Pathways

CSLYA

Comments on ortholog(s)

High-scoring ortholog of human GLO1 (1 Drosophila to 1 human). Dmel\Glo1 shares 69% identity and 81% similarity with the human gene.

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 (14 groups)

Glo1

protein-protein

Interacting group

Assay

References

Glo1 - Aldo

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - AnxB10

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Ar2

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - CG2004

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - CG2852

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - CG14715

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - EndoGI

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - fabp

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Fkbp14

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - GstO3

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Ntf-2

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Pgd

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Sh3β

experimental knowledge based

(Guruharsha et al., 2011)

Glo1 - Uch

experimental knowledge based

(Guruharsha et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)

Glo1

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Glo1^KO

model of type 2 diabetes mellitus

CEA

(Moraru et al., 2018)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Glo1^KK109109

exacerbates Parkinson's disease

modeled by Hsap\SNCA^UAS.cFa

(Vicente Miranda et al., 2017)

exacerbates Huntington's disease

modeled by Hsap\HTT^Q93.ex1.UAS

(Vicente Miranda et al., 2016)

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

Glo1^GD12888

P{GD12888}

w¹¹¹⁸; P{GD12888}v26832

y¹ sc^* v¹ sev²¹; P{TRiP.HMC06400}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Glo1^KO

amorphic allele - molecular evidence

P-element activity

References (3)

Report Sections

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