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Fasting blood glucose and serum insulin concentrations were significantly lower in the LFD+VEH treated control group compared with all other groups. The mean levels of both serum glucose and insulin were next higher in the LFD+NDEA group, followed by the HFD group. The HFD+NDEA treated rats had the highest mean serum glucose and insulin levels. Correspondingly, serum leptin levels were significant
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Xidative stress and neurodegeneration. Cerebellar protein homogenates were used to measure (A) GSK-3b; (B) phospho (p)-GSK-3b; (C) GFAP; (D) GAPDH; (E) HNE; (F) malondialdehyde, MDA; (G) Nitrotyrosine, N-TYR; or (H) b-Actin; by direct binding ELISA. Immunoreactivity was detected with HRP-conjugated secondary antibody and Amplex Red soluble fluorophor. Fluorescence light units (FLU) were measured (
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Of age. Biochem Mol Biol Int 1998, 44(1):1-7. 38. Haan MN: Therapy Insight: type 2 diabetes mellitus and the risk of lateonset Alzheimer's disease. Nat Clin Pract Neurol 2006, 2(3):159-166. 39. Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, Degroodt W, Mehta P, Craft S: Intranasal insulin improves cognition and modulates beta-amyloid in earl
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S performed using the ABC method, and revealed with DAB (brown precipitate)-see Experimental Procedures. Sections were lightly counterstained with Hematoxylin (blue) to help reveal the tissue architecture. Cerebellar layers: ml = molecular layer; pc = Purkinje cell layer; gc = granule cell layer; wm = white matter. Note focal pc loss in A2, and large zones of pc loss in A3 and A4. (Original Magnif
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E formation of DNA and protein adducts [105-107] that can serve as persistent sources of oxidative stress, and cause further DNA damage and protein dysfunction. Recently, we demonstrated a role for ceramidemediated neurodegeneration in a model of diet-induced obesity with T2DM [45], and showed that in vitro ceramide exposure causes neurodegeneration with impairments in neuronal viability, energy m
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R protein; AbPP-Ab: amyloid-b peptide; AChE: acetylcholinesterase; AD: Alzheimer's disease; CER: Ceramide synthase; ChAT: choline acetyltransferase; ELISA: enzyme-linked immunosorbant assay; GFAP: glial fibrillary acidic protein; GSK-3b: glycogen synthase kinase-3b; H E: hematoxylin and eosin; HFD: high fat diet; HNE: 4-hydroxy-2-nonenal; HRP: horseradish peroxidase; i.p.: intraperitoneal; IGF: In
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Ration have soared over the past several decades, suggesting that exposures rather than genetics dictate their etiologies. Our over-arching hypothesis is that shifts in lifestyles and economics have led us to chronically consume excess fat, and get exposed to agents that cause insulin resistance. Consideration given to potential pathogenic agents was focused by the experimental evidence showing th
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Ation with impairments in insulin/IGF signaling mechanisms, and deficits in cholinergic and neuronal cytoskeletal gene and protein expression in brain, whereas chronic HFD feeding alone produces more restrictive deficits in insulin/IGF signaling mechanisms with reduced ChAT expression and increased oxidative stress. The combined exposures caused overlapping structural and molecular abnormalities t