title: Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release.
abstract: OBJECTIVE
  To evaluate the effects of insulin on vascular cell adhesion molecule-1 expression by cultured human vascular endothelial cells and soluble vascular cell adhesion molecule-1 release in vivo.
  
  
  METHODS
  Human vascular endothelial cells derived from umbilical cord veins were incubated with either insulin (from 10(-6) to 10(-9) mol/l) or tumour necrosis factor-alpha (5 ng/ml) for 6 to 24 h. Plasma soluble vascular cell adhesion molecule-1 concentrations were evaluated in 12 non-insulin-dependent diabetic patients (8 men, 4 women, mean age 47.1 +/- 7.7 years) and 12 healthy volunteers matched for age, sex and weight (7 men, 5 women, mean age 42.2 +/- 7.2 years) before and after a 2-h euglycaemic hyperinsulinaemic clamp.
  
  
  RESULTS
  Transcriptional activities of nuclear factor-kappaB luciferase and vascular adhesion molecule-1 luciferase statistically significantly increased after incubation with tumour necrosis factor-alpha. By contrast, a slight increment of nuclear factor-kappaB luciferase (mean: 1.8 +/- 0.3 fold) but not of vascular cell adhesion molecule-1 luciferase transcriptional activities were detected in cells stimulated with insulin. Soluble vascular cell adhesion molecule-1 concentrations in cell supernatants increased after tumour necrosis factor-alpha but not insulin stimulation. In vivo, baseline plasma soluble vascular cell adhesion molecule-1 concentrations were higher (p = 0.03) in non-insulin-dependent patients (708.7 +/- 97.4 microg/l) than controls (632.1 +/- 65.2 microg/l) but were not related to fasting insulin concentrations and did not change during insulin infusion.
  
  
  CONCLUSIONS
  The increased concentrations of circulating soluble vascular cell adhesion molecule-1 indicates that the vascular endothelium is activated in non-insulin dependent diabetic patients. Our in vitro and in vivo findings show that vascular cell adhesion molecule-1 activation cannot be due to hyperinsulinaemia. [Diabetologia (1999) 42: 1235-1239]
authors.affiliation: University "La Sapienza", Andrea Cesalpino Foundation, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Mattia
authors.forename: M C
authors.initials: MC
authors.lastname: Bravi
authors.forename: A
authors.initials: A
authors.lastname: Costanzo
authors.forename: O
authors.initials: O
authors.lastname: Laurenti
authors.forename: M
authors.initials: M
authors.lastname: Cassone Faldetta
authors.forename: A
authors.initials: A
authors.lastname: Armiento
authors.forename: O
authors.initials: O
authors.lastname: De Luca
authors.forename: C
authors.initials: C
authors.lastname: Ferri
mesh_terms: D000328:Adult; D001786:Blood Glucose; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000097:blood*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1