HIGH GLUCOSE-LEVELS MODULATE EICOSANOID PRODUCTION IN UTERINE AND PLACENTAL TISSUE FROM NON-INSULIN-DEPENDENT DIABETIC RATS DURING LATE PREGNANCY

Severe uterine and placental disturbances have been described in diabe tes pathology. The relative severity of these changes appears to corre late with high glucose levels in the plasma and incubating environment . In order to characterize changes in eicosanoid production we compare d uterine and placental arachidonic acid conversion from control and n on-insulin-dependent diabetes mellitus (NIDDM) rats on day 21 of pregn ancy, into different prostanoids, namely PGE(2), PGF(2 alpha), TXB2 (i ndicating the production of TXA(2)) and 6-keto-PGF(1) (indicating the generation of PGI(2)). PGE(2), PGF(2 alpha), and TXB2 production was h igher and 6-keto-PGF(1 alpha) was similar in diabetic compared to cont rol uteri. PLA, activity was found diminished in the NIDDM uteri in co mparison to control. A role for PLA(2) diminution as a protective mech anism to avoid prostaglandin overproduction in uterine tissue from NID DM rats is discussed. Placental tissues showed an increment in TXB2 ge neration and a decrease in 6-keto PGF(1 alpha) level in diabetic rats when compared to control animals. Moreover, when control uterine tissu e was incubated in the presence of elevated glucose concentrations (22 mM), similar generation of 6-keto PGF(1 alpha) and elevated productio n of PGE(2), PGF(2 alpha) and TXB2 were found when compared to those i ncubated with glucose 11 mM. Placental TXB2 production was higher and 6-keto PGF(1 alpha) was lower when control tissues were incubated in t he presence of high glucose concentrations. However, high glucose was unable to modify uterine or placental prostanoid production in diabeti c rats. We conclude that elevated glucose levels induced an abnormal p rostanoid profile in control uteri and placenta, similar to those obse rved in non-insulin-dependent diabetic tissues.