RGD Reference Report - Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome. - Rat Genome Database

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Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome.

Authors: Toots, Maarja  Seppa, Kadri  Jagomäe, Toomas  Koppel, Tuuliki  Pallase, Maia  Heinla, Indrek  Terasmaa, Anton  Plaas, Mario  Vasar, Eero 
Citation: Toots M, etal., Sci Rep. 2018 Jul 5;8(1):10183. doi: 10.1038/s41598-018-28314-z.
RGD ID: 150519890
Pubmed: PMID:29976929   (View Abstract at PubMed)
PMCID: PMC6033861   (View Article at PubMed Central)
DOI: DOI:10.1038/s41598-018-28314-z   (Journal Full-text)

Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations in the WFS1 (Wolframin1) gene. The syndrome first manifests as diabetes mellitus, followed by optic nerve atrophy, deafness, and neurodegeneration. The underlying mechanism is believed to be a dysregulation of endoplasmic reticulum (ER) stress response, which ultimately leads to cellular death. Treatment with glucagon-like peptide-1 (GLP-1) receptor agonists has been shown to normalize ER stress response in several in vitro and in vivo models. Early chronic intervention with the GLP-1 receptor agonist liraglutide starting before the onset of metabolic symptoms prevented the development of glucose intolerance, improved insulin and glucagon secretion control, reduced ER stress and inflammation in Langerhans islets in Wfs1 mutant rats. Thus, treatment with GLP-1 receptor agonists might be a promising strategy as a preventive treatment for human WS patients.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SD-Wfs1em1PtsnRatglucose intolerance treatmentIMPliraglutide RGD 
WFS1Humanglucose intolerance treatmentISOWfs1 (Rattus norvegicus) RGD 
Wfs1Ratglucose intolerance treatmentIMPliraglutide RGD 
Wfs1Mouseglucose intolerance treatmentISOWfs1 (Rattus norvegicus) RGD 
Wfs1em1PtsnRatglucose intolerance treatmentIMPliraglutide RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Wfs1  (wolframin ER transmembrane glycoprotein)
Wfs1em1Ptsn  (wolframin ER transmembrane glycoprotein; ZFN induced mutant 1)

Genes (Mus musculus)
Wfs1  (wolframin ER transmembrane glycoprotein)

Genes (Homo sapiens)
WFS1  (wolframin ER transmembrane glycoprotein)

Strains
SD-Wfs1em1Ptsn  (NA)


Additional Information