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