title: Effects of glucose and insulin on secretion of amyloid-β by human adipose tissue cells.
abstract: 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.
  
  
  
  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.
authors.affiliation: Department of Medicine Endocrine Unit, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Tharp
authors.affiliation: Department of Medicine Endocrine Unit, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Florida Hospital Sanford/Burnham Translational Research Institute for Metabolism and Diabetes, Orlando, Florida, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Smith
authors.affiliation: Florida Hospital Sanford/Burnham Translational Research Institute for Metabolism and Diabetes, Orlando, Florida, USA.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Jones
authors.affiliation: Florida Hospital Sanford/Burnham Translational Research Institute for Metabolism and Diabetes, Orlando, Florida, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: Florida Hospital Sanford/Burnham Translational Research Institute for Metabolism and Diabetes, Orlando, Florida, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D011972:Receptor, Insulin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose