title: Repetitive hypoglycaemia increases serum adrenaline and induces monocyte adhesion to the endothelium in rat thoracic aorta.
abstract: OBJECTIVE
  Severe hypoglycaemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect and mechanism of hypoglycaemia on the progression of atherosclerosis remains largely unknown. As a first step towards elucidating the above, we investigated the effect of hypoglycaemia on monocyte-endothelial interaction.
  
  
  METHODS
  Insulin was injected intraperitoneally once every 3 days for 5 weeks in Goto-Kakizaki rats, a non-obese rat model of type 2 diabetes. We counted the number of monocytes adherent to the endothelium of thoracic aorta as an index of early atherosclerogenesis. Cultured HUVEC were used to investigate the mechanism of action.
  
  
  RESULTS
  Insulin treatment increased the number of monocytes adherent to the vascular endothelium. This increase was abrogated by injection of glucose with insulin. Amosulalol, an α-1 and β-adrenoreceptor antagonist, suppressed monocyte adhesion to endothelium and levels of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelial surface, which had been enhanced by insulin-induced hypoglycaemia. In HUVEC, adrenaline (epinephrine) significantly increased nuclear translocation of nuclear factor-κB (NF-κB) p65 and levels of adhesion molecules, effects that were abrogated following addition of SQ22536, a specific adenyl cyclase inhibitor.
  
  
  CONCLUSIONS
  Our data indicate that repetitive hypoglycaemia induced by insulin enhanced monocyte adhesion to endothelial cells in Goto-Kakizaki rat aorta through enhanced adrenaline activity and that the latter stimulated intracellular cAMP, leading to nuclear translocation of NF-κB with subsequent production of adhesion molecules in endothelial cells.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: W L
authors.initials: WL
authors.lastname: Jin
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.forename: T
authors.initials: T
authors.lastname: Mita
authors.forename: H
authors.initials: H
authors.lastname: Goto
authors.forename: A
authors.initials: A
authors.lastname: Kanazawa
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: F
authors.initials: F
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Fujitani
authors.forename: T
authors.initials: T
authors.lastname: Hirose
authors.forename: R
authors.initials: R
authors.lastname: Kawamori
authors.forename: H
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood*; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology*; D008297:Male; D009000:Monocytes / Q000166:cytology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004837:Epinephrine