Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes?

By Eric M. Steen, Benjamin M. Terry, Enrique J. Rivera, J. Cannon, Thomas R. Neely, Rosemarie Tavares, X. J. Xu, J. Wands, S. M. de la Monte. Journal of Alzheimer's Disease, 2005

1,682 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/13220ce65f651806480731fb58e525e5427d26db

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Citations in the corpus

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function (2014, background): “Patients with AD exhibit reduced expression and activation of IR, IGF-1R, and IRS-1 proteins in the brain, in particular in the hippocampus and hypothalamus, as well as increased serine phosphorylation in IRS-1, which is generally regarded as inhibitory (78,79).”
Identification of miRNA Changes in Alzheimer's Disease Brain and CSF Yields Putative Biomarkers and Insights into Disease Pathways (2008, positive): “Regulation of brain insulin levels and the loss of insulin receptor signaling molecules have been linked to amyloid-mediated pathogenesis as well as memory [60,70].”
Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. (2012, positive): “A number of the findings at upstream levels of the pathway are consistent with insulin resistance as defined above, notably decreased basal activation of IRs (28); reduced insulin binding of the IR, even early in the disorder (27); increased serine phosphorylation (pS) of IRS-1 (29, 33, 37); and red”
BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE (2010, background): “Furthermore, the insulin receptor is present in several brain regions and is linked to neuronal activity [81–84].”
Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. (2013, background): “Impaired insulin signaling pathway increases Ab accumulation in T2DM patients (Steen et al., 2005).”
Inflammation, Defective Insulin Signaling, and Mitochondrial Dysfunction as Common Molecular Denominators Connecting Type 2 Diabetes to Alzheimer Disease (2014, background): “AD brains exhibit defective insulin signaling, altered levels and/or aberrant activation of components of the insulin signaling pathway, and, importantly, decreased responsiveness to insulin (35,36,38).”
Inflammation and metabolic disorders (2006, background): “It has even been proposed that defective insulin action in the nervous system be labelled type 3 diabetes, particularly in the context of Alzheimer's diseas”
Inflammation as a central mechanism in Alzheimer's disease (2018, background): “[256] Steen E, Terry BM, J Rivera E, Cannon JL, Neely TR, Tavares R, et al.”
Trends in insulin resistance: insights into mechanisms and therapeutic strategy (2022, background): “For example, major abnormalities in AD brains include decreased mRNA and protein expression levels of insulin, insulin receptors, insulin receptor substrate 1 (IRS1) and IGF1/2, in addition to reduced protein indicators of downstream insulin signaling activity (including phosphorylated AKT (pAKT) an”
Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: Link to brain reductions in acetylcholine (2005, neutral): “Recently, we demonstrated that brains with advanced AD exhibit major abnormalities in insulin and IGF polypeptideand receptor expression,and reduced downstream signaling mechanisms that mediate neuronal survival [23].”
Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “336,337 Lower levels of Akt activation weaken the inhibition of glycogen synthase kinase-3 (GSK-3), which in turn positively affects the phosphorylation of tau protein and the production of A β .”