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Effects of glucose and insulin on secretion of amyloid‐β by human adipose tissue cells
Author(s) -
Tharp William G.,
Gupta Dhananjay,
Smith Joshua,
Jones Karen P.,
Jones Amanda M.,
Pratley Richard E.
Publication year - 2016
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21494
Subject(s) - adipose tissue , medicine , endocrinology , insulin resistance , insulin receptor , adipose tissue macrophages , insulin , type 2 diabetes , microdialysis , biology , glucose uptake , diabetes mellitus , central nervous system
Objective Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping 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. Methods 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. Results 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. Conclusions 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.