Tharp, William G., Gupta, Dhananjay, Smith, Joshua, Jones, Karen P., Jones, Amanda M., Pratley, Richard E.
funding text
WGT was supported by an individual fellowship award from the National Institute of Diabetes and Digestive and Kidney Diseases (F30 DK084605).
abstract
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.