Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI(2)), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin-1 in plasma (p), and NO and PGI(2) mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years. "Placebo clamping" with NaCl infusion was performed in a subgroup of 5/51 women. During euglycaemic hyperinsulinaemic clamping, p-endothelin-1 decreased (from 3.3 +/- 0.2 pg/ml to 2.4 +/- 0.2 pg/ml; p<0.01), whereas p-neopterin (from 5.0 +/- 1.1 nmol/l to 6.2 +/- 1.4 nmol/l; p<0.001) and both intraplatelet cGMP (from 0.61 +/- 0.03 to 0.68 +/- 0.03 pmol/10(9) platelets; p<0.05) and cAMP (from 4.00 +/- 0.14 to 4.76 +/- 0.20 pmol/10(9) platelets; p<0.001) increased. Increases in cGMP (from 0.79 +/- 0.0.05 to 1.07 +/- 0.15 pmol/10(9) platelets; p = 0.14) and cAMP (from 4.76 +/- 0.15 to 5.52 +/- 0.36 pmol/10(9) platelets; p = 0.08) also occurred during NaCl infusion, whereas neopterin and endothelin-1 values were unchanged. In conclusion, insulin administration was associated with decreasing p-endothelin-1 levels and increasing levels of p-neopterin and intraplatelet cyclic nucleotides in accordance with vasodilatation and monocyte activation.