Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9.
OBJECTIVE
We recently demonstrated a potent anti-inflammatory and thus a potential antiatherogenic effect of insulin in human aortic endothelial cells and mononuclear cells at physiologically relevant concentrations. We have now further investigated the anti-inflammatory suppressive action of insulin on vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. VEGF and MMP-9 play a central regulatory role in angiogenesis, contribute to the pathogenesis of proliferative retinopathy, and have also been found to accelerate atherosclerosis.


METHODS
Insulin was infused (2 IU/h) in 5% dextrose (100 ml/h) and KCl (8 mmol/h) into 10 fasting, obese, nondiabetic subjects for 4 h. Subjects were also infused with 5% dextrose without insulin and with saline on two separate occasions. Blood samples were obtained at 0, 2, 4, and 6 h.


RESULTS
Plasma insulin concentrations increased from a basal level of 12.5 +/- 2.2 to 28.2 +/- 3.3 micro U/ml at 2 h and 24.4 +/- 3.7 micro U/ml at 4 h after insulin infusion. VEGF concentration decreased from 307.2 +/- 163.8 pg/ml (100%) at 0 h to 73.5 +/- 20.9% of the basal level at 2 h and 67.1 +/- 23.2% at 4h. Plasma MMP-9 concentrations decreased from 375 +/- 196.3 ng/ml (100%) at 0 h to 83 +/- 22% of the basal level at 2 h and to 82 +/- 21% of the basal level at 4 h (P < 0.05). Dextrose infusion alone did not change plasma VEGF concentration. However, plasma MMP-9 concentration increased significantly at 4 h following dextrose infusion alone (P < 0.05). Saline infusions without insulin caused no alteration in glucose, insulin, VEGF, or MMP-9.


CONCLUSIONS
These observations may have implications for a potential antiretinopathic and antiatherosclerotic effect of insulin in the long term.
Dandona
Paresh
P
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York, USA. pdandona@kaleidahealth.org
Aljada
Ahmad
A
Mohanty
Priya
P
Ghanim
Husam
H
Bandyopadhyay
Arindam
A
Chaudhuri
Ajay
A
D000328:Adult; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D012965:Sodium Chloride / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood*
D007328:Insulin; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D012965:Sodium Chloride; D020780:Matrix Metalloproteinase 9; D005947:Glucose