title: Deficient hippocampal insulin signaling and augmented Tau phosphorylation is related to obesity- and age-induced peripheral insulin resistance: a study in Zucker rats.
abstract: 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-3β (glycogen synthase kinase 3β) 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Špolcová
authors.forename: Barbora
authors.initials: B
authors.lastname: Mikulášková
authors.forename: Katarína
authors.initials: K
authors.lastname: Kršková
authors.forename: Lucia
authors.initials: L
authors.lastname: Gajdošechová
authors.forename: Štefan
authors.initials: Š
authors.lastname: Zórad
authors.forename: Rafał
authors.initials: R
authors.lastname: Olszanecki
authors.forename: Maciej
authors.initials: M
authors.lastname: Suski
authors.forename: Beata
authors.initials: B
authors.lastname: Bujak-Giżycka
authors.forename: Blanka
authors.initials: B
authors.lastname: Železná
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Prague, 166 10, Czech Republic. maletin@uochb.cas.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D005951:Glucose Tolerance Test; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011924:Rats, Zucker; D015398:Signal Transduction; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; C489131:Mapt protein, rat; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3