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Stem Cell Approach to Investigating the Phenomenon of Brain Insulin Resistance

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What is the evidence that “brain insulin resistance” is a consistent feature of Alzheimer’s disease? The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened a summit in the summer of 2015 wherein the major question for new research focuses on establishing molecular and physiological criteria for “brain insulin resistance.” Several investigators have proposed that brain insulin resistance is a feature of human AD. Some have gone so far as to propose that AD be considered as “Type 3 diabetes.” The only direct study of insulin-signaling in AD brain tissue was that reported by Talbot and colleagues. We propose to apply induced pluripotent stem cell technology to study insulin signaling in neurons, astrocytes and mixed cultures from subjects with Donohue’s extreme insulin resistance (DIR) syndrome, in whom mutations in the insulin receptor abrogate all insulin signaling.