Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release

Diabetologia. 1999 Oct;42(10):1235-9. doi: 10.1007/s001250051297.

Abstract

Aims/hypothesis: 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.

Conclusion/interpretation: 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]

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Female
  • Gene Expression / drug effects
  • Genes, Reporter
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin / blood
  • Insulin / pharmacology*
  • Male
  • Middle Aged
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • Time Factors
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / blood*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1