title: Insulin suppresses the expression of amyloid precursor protein, presenilins, and glycogen synthase kinase-3beta in peripheral blood mononuclear cells.
abstract: OBJECTIVE
  Our objective was to determine whether peripheral blood mononuclear cells express amyloid precursor protein (APP) and other mediators involved in the pathogenesis of Alzheimer's disease and whether their expression is suppressed by insulin.
  
  
  METHODS
  Ten obese type 2 diabetic patients were infused with insulin (2 U/h with 100 ml 5% dextrose/h) for 4 h. Patients were also infused with 5% dextrose/h or normal physiological saline for 4 h, respectively, on two other days as controls. Blood samples were obtained at 0, 2, 4, and 6 h.
  
  
  RESULTS
  Insulin infusion significantly suppressed the expression of APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3β in peripheral blood mononuclear cells. Dextrose and saline infusions did not alter these indices. Insulin infusion also caused significant parallel reductions in nuclear factor-κB binding activity and plasma concentrations of serum amyloid A and intercellular adhesion molecule-1.
  
  
  CONCLUSIONS
  A low dose infusion of insulin suppresses APP, presenilin-1, presenilin-2, and glycogen synthase kinase-3β, key proteins involved in the pathogenesis of Alzheimer's disease, in parallel with exerting its other antiinflammatory effects.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA. pdandona@KaleidaHealth.org
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
authors.forename: Islam
authors.initials: I
authors.lastname: Mohamed
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Chang Ling
authors.initials: CL
authors.lastname: Sia
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhindsa
authors.forename: Sonny
authors.initials: S
authors.lastname: Dandona
authors.forename: Antoine
authors.initials: A
authors.lastname: Makdissi
authors.forename: Ajay
authors.initials: A
authors.lastname: Chaudhuri
mesh_terms: D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D001786:Blood Glucose; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D053763:Presenilins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D007328:Insulin; D053763:Presenilins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3