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Impact of antidiabetic substances to development of insulin resistance and neurodegenerative changes in mouse models of type 2 diabetes
Mikulášková, Barbora ; Čabala, Radomír (advisor) ; Kuneš, Jaroslav (referee)
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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Impact of antidiabetic substances to development of insulin resistance and neurodegenerative changes in mouse models of type 2 diabetes
Mikulášková, Barbora ; Čabala, Radomír (advisor) ; Kuneš, Jaroslav (referee)
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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Central insulin signaling and phosphorylation of Tau protein in rat model of type 2 diabetes
Kasperová, Barbora Judita ; Čabala, Radomír (advisor) ; Mládková, Jana (referee)
Diabetes mellitus 2. typu (DM2) a Alzheimerova nemoc (AN) jsou jedny z nejzávažnějších nemocí naší doby. Právě DM2, spolu s obezitou a nedostatkem pohybu jsou jedny z nejrizikovějších faktorů vedoucí k poruchám kognitivních funkcí a rozvoji demence. Při rozvoji AN dochází k patologickým změnám v mozku. Dochází ke vzniku nerozpustných extracelulárních plaků amyloidního beta peptidu a hyperfosforylaci proteinu Tau. Tato bakalářská práce studuje inzulínovou signalizační kaskádu a fosforylaci proteinu Tau v hipokampech 12ti týdenních ZDF (Zucker Diabetic Fatty) potkanů, zvířecím modelu DM2, v brzkém věku života. Z inzulínové signalizační kaskády bylo detekováno signifikantně nižší množství inzulínového receptoru v hipokampech ZDF potkanů ve srovnání s kontrolami. U ostatních kinas této kaskády (PDK-1, Akt) nebyl nalezen rozdíl jak v celkovém, tak fosforylovaném/aktivovaném proteinu v hipokampech ZDF potkanů a kontrol. Rovněž u fosforylace/aktivace kinas proteinu Tau (GSK-3β, ERK, JNK) a fosforylace/aktivace proteinu Tau na několika epitopech (Ser396, Thr212, Thr231) nebyly pozorovány žádné signifikantní rozdíly mezi ZDF potkany a kontrolami. V hipokampech 12ti týdenních ZDF potkanů, ačkoliv silně hyperglykemických a obézních, nebyly zaznamenány změny v efektivitě inzulínové signalizační kaskády ani...
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