title: The influence of insulin infusion on the metabolism of amyloid β peptides in plasma.
abstract: BACKGROUND
  Accumulating body of evidence suggests pathophysiologic links between Alzheimer's disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid β (Aβ) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady-state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity.
  
  
  OBJECTIVE
  The aim of this study was to analyze the influence of insulin on the plasma concentrations of Aβ peptides.
  
  
  METHODS
  Blood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aβ1-42, Aβx-42, Aβ1-40, and Aβx-40 were performed with multiplexing technology. Furthermore, concentrations of the Aβ peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy.
  
  
  RESULTS
  When applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aβ42 (full length and N-terminally shortened) but not of Aβ40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aβx-40). We did not observe differences between Aβ peptide concentrations in healthy subjects and those in type 1 DM patients.
  
  
  CONCLUSIONS
  Infusion of insulin in nonphysiologic high doses increases plasma concentrations of Aβ peptides; in case of Aβ40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aβ peptides to the degradation of insulin.
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Białystok, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Karczewska-Kupczewska
authors.forename: Natalia
authors.initials: N
authors.lastname: Lelental
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Adamska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikołajuk
authors.forename: Irina
authors.initials: I
authors.lastname: Kowalska
authors.forename: Maria
authors.initials: M
authors.lastname: Górska
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Marek
authors.initials: M
authors.lastname: Strączkowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Lewczuk
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000097:blood*; D001667:Binding, Competitive; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy; D004357:Drug Synergism; D004655:Emulsions / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007339:Insulysin / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D010743:Phospholipids / Q000097:blood / Q000494:pharmacology; D013024:Soybean Oil / Q000097:blood / Q000494:pharmacology; D013379:Substrate Specificity; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007328:Insulin; D007339:Insulysin; D010446:Peptide Fragments; D010743:Phospholipids; D013024:Soybean Oil; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C545823:soybean oil, phospholipid emulsion