Effects of Glucose and Insulin on Secretion of Amyloid-β by Human Adipose Tissue Cells

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-beta (A beta) precursor protein and associated beta- and gamma-secretases are expressed in adipose tissue. A beta precursor protein is up-regulated with obesity and correlated to insulin resistance. A beta may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and A beta 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 A beta in conditioned media. A beta was measured in vivo using adipose tissue microdialysis. Results: A beta secretion was increased by glucose and insulin in vitro. Adipose tissue microdialysates contained A beta. Adipocytes treated with A beta had decreased expression of insulin receptor substrate-2 and reduced Akt-1 phosphorylation. Conclusions: A beta was made by adipose tissue cells in vitro at concentrations similar to in vivo measurements. Regulation of A beta production by glucose and insulin and effects of A beta on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.