Impact of antidiabetic substances to development of insulin resistance and neurodegenerative changes in mouse models of type 2 diabetes

Master thesis Czech RESTRICTED
Mikulášková, Barbora (2014)
  • Subject: phosphorylation of Tau; Alzheimer disease; diabetic mice; insulin resistence; rezistence k inzulínu; Alzheimerova choroba; diabetické myši; fosforylace Tau
    mesheuropmc: mental disorders

Numerous epidemiological and experimental studies have shown that patients suffering from metabolic disorders such as type 2 diabetes mellitus (TDM2), insulin resistance or obesity are at a higher risk of cognitive functions impairment and developing Alzheimer's disease (AD). Impairment of insulin signalling in the brain could contribute to two pathological changes which leads to AD development that include insoluble senile plaques and neurofibrillary tangles, containing an abnormally hyperphosphorylated tau protein (Tau). This work is focused on investigating of insulin signaling in hippocampi in the brains of mice models of insulin resistence, impact of disturbed insulin signaling on hyperphosphorylation of Tau, and possible benefical efect of insulin sensitizing agents on insulin signaling and Tau phosphorylation in the hippocampi of diabetic mice. The first, we examined insulin signaling and phosphorylation of Tau in hippocampi in two mouse models of TDM2 - lipodystrofic A-ZIP F-1 mice and monosodium glutamate obese mice (MSG mice). We did not observe any changes in insulin signaling and Tau phosphorylation in hippocampi of A-ZIP F-1 mice compared to controls. In the hippocampi of MSG mice there was attenuated phosphorylation of kinases of insulin signalling including Ser9 of glycogen synthase...
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