Plasma Prostaglandin Levels in Rats with Diabetes Mellitus and Diabetic Ketoacidosis

Abstract

We studied by radioimmunoassay the plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E2 (the stable metabolite of PGE2), 6-keto-PGFUt[the stable breakdown product of prostacyclin (PGI2)], and thromboxane (TX) B2 (the stable breakdown product of TXA2) in normal rats and rats with nonketotic diabetes mellitus (DM) or diabetic ketoacidosis (DKA). The plasma levels of the PGE2, PGI2, and TXA2 derivatives were markedly elevated in rats with DKA. The level of 13,14-dihydro-15-keto-PGE2 (0.298 ± 0.056 ng/ml, N = 34) was sixfold higher, the level of 6-keto-PGF1α (0.378 ± 0.049 ng/ml, n = 33) was twofold higher, and that of TXB2 (0.346 ± 0.046 ng/ml, n = 34) was 50% higher in rats with DKA than in normal rats. The plasma level of the PGI2 derivative was also elevated in rats with DM. The level of 6-keto-PGF1α (0.310 ± 0.050 ng/ml) was nearly as high in animals with DM as in those with DKA. The level of 13,14-dihydro-15-keto-PGE2 was not elevated and that of TXB2 was reduced in animals with DM. In response to insulin and to 5-methylpyrazole-3-carboxylic acid, two potent antilipolytic agents, the levels of 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1α, decreased significantly in rats with DKA. Adipocytes produce large quantities of PGE2 and PGI2 during norepinephrine-induced lipolysis. DKA is a situation par excellence of high catecholamine and low insulin levels, just the circumstances required for accelerated lipolysis and maximal production of PGE2 and PGI2 by the adipocyte. The adipocyte may be an important source of the high plasma levels of the PGE2 and PGI2 derivatives present in rats with DKA and of the elevated levels of the PGI2 derivative present in animals with DM. The ability of both insulin and 5-methylpyrazole-3-carboxylic acid to decrease the levels of 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1α supports this view. The high plasma levels of the PGE2, PGI2, and TXA2 derivatives in DKA and of the PGI2 derivative in DM raise the possibility that high levels of all three parent compounds may circulate in DKA and high levels of PGI2 may circulate in DM. The suppression of the elevated levels of 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1α in DKA by two structurally unrelated antilipolytic agents suggests that the adipocyte may be a major source of the high plasma levels of both derivatives in this disorder.