title: Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women.
abstract: 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.
authors.affiliation: Department of Vascular and Renal Diseases, University of Lund, University Hospital Malmö, Sweden. Anders.Gottsater@medforsk.mas.lu.se
authors.forename: A
authors.initials: A
authors.lastname: Gottsäter
authors.forename: M
authors.initials: M
authors.lastname: Rendell
authors.forename: I
authors.initials: I
authors.lastname: Anwaar
authors.forename: F
authors.initials: F
authors.lastname: Lindgärde
authors.forename: U L
authors.initials: UL
authors.lastname: Hulthén
authors.forename: I
authors.initials: I
authors.lastname: Mattiasson
mesh_terms: 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*
chemical_list: D019332:Endothelin-1; D018836:Inflammation Mediators; D007328:Insulin; D019798:Neopterin; D000242:Cyclic AMP; D006152:Cyclic GMP