Plasma eicosanoid levels in rats with nonketotic diabetes mellitus: effect of severity

Nonketotic diabetes mellitus (DM) is associated with increased platelet production of thromboxane (TX) A2 and decreased endothelial production of prostacyclin (prostaglandin [PG]I2), but measurements of stable derivatives of these substances in the circulation have yielded discordant results. We studied the relationship between the severity of nonketotic DM and the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha, and TXB2 (stable derivatives of PGE2, PGI2, and TXA2, respectively) in rats, using three commonly employed doses of streptozotocin (40, 50, and 60 mg/kg body weight) to induce nonketotic DM of varying severity. Small differences in the severity of DM were associated with considerable differences in the plasma levels of 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1 alpha but not TXB2. Each eicosanoid responded differently to variations in the severity of DM. The plasma 13,14-dihydro-15-keto-PGE2 level was significantly lower than normal in the rats given 40 mg/kg streptozotocin, was unchanged from normal in the rats given 50 mg/kg and was significantly higher than normal in the rats given 60 mg/kg. The plasma 6-keto-PGF1 alpha level was significantly increased in rats given 40 mg/kg and 60 mg/kg, but was unchanged in those given 50 mg/kg. The plasma TXB2 level was not significantly different from normal in any one of the three groups of rats with nonketotic DM. The effect of severity on the plasma levels of the PGE2 and PGI2 derivatives is unexplained, but may reflect the origin of these derivatives from diverse organs and tissues, and the differing effects of abnormal metabolic factors (eg, fatty acids, glucose, insulin, pH) on the synthesis of these derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)