Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:58

Article

Velazquez, Ramon¹  Tran, An¹  Ishimwe, Egide²  Denner, Larry³  Dave, Nikhil¹  Oddo, Salvatore^1,4  Dineley, Kelly T.² 

[1] Arizona State Univ, Banner Neurodegenerat Dis Res Ctr, Biodesign Inst, Tempe, AZ 85287 USA

[2] Univ Texas Med Branch, Dept Neurol, Mitchell Ctr Neurodegenerat Dis, Galveston, TX 77555 USA

[3] Univ Texas Med Branch, Internal Med, Mitchell Ctr Neurodegenerat Dis, Galveston, TX 77555 USA

[4] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA

关键词: Alzheimer's disease;    Type two diabetes;    Tg2576;    3xTg-AD;    Insulin resistance;    Glucose tolerance test;    Aging;    Neurodegeneration;    Energy metabolism;   

DOI  :  10.1016/j.neurobiolaging.2017.06.003

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling. (C) 2017 Elsevier Inc. All rights reserved.

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