An Investigation of the Role of Insulin Deficiency and Loss of PI3K-Akt Signaling Downstream Regulators GSK3β -CREB Signaling in the Pathogenesis of the Diabetic Brain
Date
2014-07-11
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Abstract
Our lab has developed a robust streptozotocin-induced murine model with changes analogous to those observed in human diabetic brain, and our lab has shown that replacement of insulin in the brain via intranasal delivery prevents diabetes mellitus (DM) mediated neurodegeneration. Insulin is speculated to act through activation of PI3K-Akt signaling. We hypothesized that the neurodegenerative changes and cognitive impairments observed in the chronic type 1 DM brain occur through impaired insulin-mediated phosphorylation of CREB/GSK3β, critical neuronal signals downstream of PI3K-Akt pathway and direct support of these proteins will prevent these neurodegenerative changes. A transgenic murine model with downregulation of CREB in the forebrain was used to complement interventions to attempt to rescue the chronic type 1 DM brain. Intranasal TDZD-8 was used to inhibit GSK3β in wild type mice. Our results are consistent with the hypothesis that CREB is essential for brain insulin signaling but that GSK3β might not be directly involved in this pathway.
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Neuroscience
Citation
ALRAZI, TAZRINA. (2014). An Investigation of the Role of Insulin Deficiency and Loss of PI3K-Akt Signaling Downstream Regulators GSK3β -CREB Signaling in the Pathogenesis of the Diabetic Brain (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/24919