Leukotrienes (LTs) are able to be produced by whole blood cells as well as polymorphonuclear leukocytes (PMN). To investigate whether these production rates were affected by insulin, LTs from PMN or whole blood cells were measured in 10 diabetic patients and 10 normal subjects using HPLC. The production rate of LTB4 from PMN was lower in diabetic patients than in normal subjects. When PMN were stimulated by CaI+glucose+insulin, the LTs productuin rate was significantly increased compared with that after stimulation by CaI alone in both normal subjects and diabetic patients. LTs production rats was significantly increased in a dose-dependent manner. 5-HETE release from PMN showed significant increase when PMN were stimulated by CaI+glucose+insulin. Comparing LTs release from CaI-stimulated whole blood with that after CaI+arachidonate stimulation. there was no significant difference in normal subjects. In diabetic subjects, LTC(4), LTD(4) and LTB(4) release stimulated by CaI+arachidonate was sinificantly higher than those stimulated by CaI alone. Comparing CaI with CaI+glucose+insulin as a stimulater or LTs release, the latter was significantly more potent than that of the former in both normal subjects and diabetic patients.
Blood cells obthained from diabetic patients produced less LTs, but high concentrations of insulin combined with glucose restored LTs production. Production of LTC(4) was markedly promoted by these stimulants in diabetic patents. These findings regarding insulin action suggest mechanisms in the condition of hyperinsulinemia, i. e. they induce vasoconstriction and progression of atherogenesity, related to enfothelial cell damage, and smooth muscle cell proliferation.