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 (PGI2), 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- in plasma (p), and NO and PGI2 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+/-0.05 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.
Gottsäter
A
A
Department of Vascular and Renal Diseases, University of Lund, University Hospital Malmö, Sweden. Anders.Gottsater@medforsk.mas.lu.se
Rendell
M
M
Anwaar
I
I
Lindgärde
F
F
Hulthén
U L
UL
Mattiasson
I
I
D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000008:administration & dosage*; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*
D019332:Endothelin-1; D018836:Inflammation Mediators; D007328:Insulin; D019798:Neopterin; D000242:Cyclic AMP; D006152:Cyclic GMP