Journal Article10.1007/S12035-012-8339-9
Insulin in the Brain: Sources, Localization and Functions
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TL;DR: This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation and considers the neuromodulatory and neurotrophic effects of insulin.
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Abstract: Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.
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Chronic insulinopenia/hyperglycemia decreases cannabinoid CB1 receptor density and impairs glucose uptake in the mouse forebrain.
TL;DR: A chronic decrease or lack of CB1R expression reduces glucose uptake in the mouse brain, and insulinopenia/hyperglycemia (diabetes) with intraperitoneal streptozotocin injection suggests that diabetic encephalopathy may be in part associated with lower CB 1R expression.
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TL;DR: In this paper , the authors investigated the molecular mechanisms of midnolin expression in human neuroblastoma SH-SY5Y cells and found that it was promoted by insulin via extracellular-signal-regulated kinase1/2 and phosphoinositide 3-kinase-dependent pathways.
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TL;DR: The spatial dynamics of the insulin receptor on somatodendritic membranes of live rat hippocampal neurons in culture are investigated and suggest an association of the neuronal insulin receptor with specific elements of the dendritic shaft, rather than excitatory synapses.
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Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes
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Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Jens C. Brüning,Dinesh Gautam,Deborah J. Burks,Jennifer A. Gillette,Markus Schubert,Paul C. Orban,Rüdiger Klein,Wilhelm Krone,Dirk Müller-Wieland,C. Ronald Kahn +9 more
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TL;DR: Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release, and insulin appears to be a novel modulator of the EDNO system.
Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment
Suzanne Craft,Laura D. Baker,Thomas J. Montine,Satoshi Minoshima,G. Stennis Watson,Amy Claxton,Matthew Arbuckle,Maureen Callaghan,Elaine Tsai,Stephen R. Plymate,Pattie S. Green,James B. Leverenz,Donna J. Cross,Brooke Gerton +13 more
TL;DR: These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD.
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