RGD Reference Report - Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinson's disease. - Rat Genome Database

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Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinson's disease.

Authors: Morris, JK  Zhang, H  Gupte, AA  Bomhoff, GL  Stanford, JA  Geiger, PC 
Citation: Morris JK, etal., Brain Res. 2008 Nov 13;1240:185-95. doi: 10.1016/j.brainres.2008.08.089. Epub 2008 Sep 11.
RGD ID: 10401814
Pubmed: PMID:18805403   (View Abstract at PubMed)
PMCID: PMC2666001   (View Article at PubMed Central)
DOI: DOI:10.1016/j.brainres.2008.08.089   (Journal Full-text)

Clinical evidence has shown a correlation between Parkinson's disease (PD) and Type 2 Diabetes (T2D), as abnormal glucose tolerance has been reported in >50% of PD patients. The development of insulin resistance and the degeneration of nigrostriatal dopamine (DA) neurons are both mediated by oxidative mechanisms, and oxidative stress is likely a mechanistic link between these pathologies. Although glucose uptake in neuronal tissues is primarily non-insulin dependent, proteins involved in insulin signaling, such as insulin receptor substrate 2 (IRS2) and glucose transporter 4 (GLUT4), are present in the basal ganglia. The purpose of this study was to determine whether nigrostriatal DA depletion affects measures of insulin resistance in the striatum. Six weeks after 6-hydroxydopamine (6-OHDA) infusion into the medial forebrain bundle, rats were classified as having either partial (20-65%) or severe (90-99%) striatal DA depletion. Increased IRS2 serine phosphorylation, a marker of insulin resistance, was observed in the DA-depleted striatum. Additionally, severe depletion resulted in decreased total IRS2, indicating possible degradation of the protein. Decreased phosphorylation of AKT and expression of the kinase glycogen synthase kinase-3 alpha (GSK3-alpha) was also measured in the striatum of severely DA-depleted animals. Finally, expression of heat shock protein 25 (Hsp25), which is protective against oxidative damage and can decrease stress kinase activity, was decreased in the striatum of lesioned rats. Together, these results support the hypothesis that nigrostriatal DA depletion impairs insulin signaling in the basal ganglia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GSK3AHumanParkinsonism  ISOGsk3a (Rattus norvegicus)protein:decreased expression:striatumRGD 
Gsk3aRatParkinsonism  IEP protein:decreased expression:striatumRGD 
Gsk3aMouseParkinsonism  ISOGsk3a (Rattus norvegicus)protein:decreased expression:striatumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsk3a  (glycogen synthase kinase 3 alpha)

Genes (Mus musculus)
Gsk3a  (glycogen synthase kinase 3 alpha)

Genes (Homo sapiens)
GSK3A  (glycogen synthase kinase 3 alpha)


Additional Information