Effects of Glucose and Insulin on Secretion of Amyloid-[Beta] by Human Adipose Tissue Cells

Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Over-lapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-β (Aβ) precursor protein and associated β- and γ-secretases are expressed in adipose tissue. Aβ...

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Bibliographic Details
Published in:Obesity (Silver Spring, Md.) Md.), 2016-07, Vol.24 (7), p.1471
Main Authors: Tharp, William G, Gupta, Dhananjay, Smith, Joshua, Jones, Karen P, Jones, Amanda M, Pratley, Richard E
Format: Article
Language:English
Subjects:
Adipocytes
Biopsy
Body fat
Body mass index
Catheters
Diabetes
Experiments
Fluorides
Gene expression
Hyperglycemia
Insulin
Insulin resistance
Insulin-like growth factors
Metabolism
Obesity
Proteins
Rodents
Signal transduction
Sodium
Studies
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Summary:Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Over-lapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-β (Aβ) precursor protein and associated β- and γ-secretases are expressed in adipose tissue. Aβ precursor protein is up-regulated with obesity and correlated to insulin resistance. Aβ may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and Aβ may exert effects on adipose tissue insulin receptor signaling. Human stromal-vascular cells and differentiated adipocytes were cultured with different combinations of glucose and insulin and then assayed for Aβ in conditioned media. Aβ was measured in vivo using adipose tissue microdialysis. Aβ secretion was increased by glucose and insulin in vitro. Adipose tissue microdialysates contained Aβ. Adipocytes treated with Aβ had decreased expression of insulin receptor substrate-2 and reduced Akt-1 phosphorylation. Aβ was made by adipose tissue cells in vitro at concentrations similar to in vivo measurements. Regulation of Aβ production by glucose and insulin and effects of Aβ on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.
ISSN:1930-7381
1930-739X
DOI:10.1002/oby.21494