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Deficient hippocampal insulin signaling and augmented Tau phosphorylation is related to obesity- and age-induced peripheral insulin resistance: a study in Zucker rats.

Authors: Špolcová, Andrea  Mikulášková, Barbora  Kršková, Katarína  Gajdošechová, Lucia  Zórad, Štefan  Olszanecki, Rafal  Suski, Maciej  Bujak-Gizycka, Beata  Železná, Blanka  Maletínská, Lenka 
Citation: Špolcová A, etal., BMC Neurosci. 2014 Sep 25;15:111. doi: 10.1186/1471-2202-15-111.
Pubmed: (View Article at PubMed) PMID:25257559
DOI: Full-text: DOI:10.1186/1471-2202-15-111

BACKGROUND: Insulin signaling and Tau protein phosphorylation in the hippocampi of young and old obese Zucker fa/fa rats and their lean controls were assessed to determine whether obesity-induced peripheral insulin resistance and aging are risk factors for central insulin resistance and whether central insulin resistance is related to the pathologic phosphorylation of the Tau protein.
RESULTS: Aging and obesity significantly attenuated the phosphorylation of the insulin cascade kinases Akt (protein kinase B, PKB) and GSK-3ß (glycogen synthase kinase 3ß) in the hippocampi of the fa/fa rats. Furthermore, the hyperphosphorylation of Tau Ser396 alone and both Tau Ser396 and Thr231 was significantly augmented by aging and obesity, respectively, in the hippocampi of these rats.
CONCLUSIONS: Both age-induced and obesity-induced peripheral insulin resistance are associated with central insulin resistance that is linked to hyperTau phosphorylation. Peripheral hyperinsulinemia, rather than hyperglycemia, appears to promote central insulin resistance and the Tau pathology in fa/fa rats.


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RGD Object Information
RGD ID: 13800921
Created: 2018-10-23
Species: All species
Last Modified: 2018-10-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.