Plasma Prostaglandin Levels in Rats with Diabetes Mellitus and Diabetic Ketoacidosis
Plasma Prostaglandin Levels in Rats with Diabetes Mellitus and Diabetic Ketoacidosis
复制标题
糖尿病和糖尿病酮症酸中毒大鼠血浆前列腺素水平
作者：
L. Axelrod;L. Levine
本文用放射免疫法测定了正常大鼠、非酮症糖尿病（DM）和糖尿病酮症酸中毒（DKA）大鼠血浆前列腺素E_2（13，14-dihydro-15-keto-PGE_2）、前列环素（PGI_2）的稳定分解产物6-keto-PGFUt和血栓素（TXA_2）的稳定分解产物TXB_2的含量。DKA大鼠血浆中PGE 2、PGI 2和TXA 2衍生物水平显着升高。13，14-dihydro-15-keto-PGE 2水平（0.298 ± 0.056 ng/ml，N = 34）升高6倍，6-keto-PGF 1 α水平升高TXB_2（0.346 ± 0.046ng/ml，n = 34）较正常大鼠高50%。糖尿病大鼠血浆PGI 2衍生物水平也升高。DM组6-keto-PGF_（1 α）水平（0.310 ± 0.050 ng/ml）与DKA组接近。DM动物血浆13，14-dihydro-15-keto-PGE_2水平不升高，TXB_2水平降低。在胰岛素和5-甲基吡唑-3-羧酸的作用下，DKA大鼠中两种有效的抗脂解剂13，14-二氢-15-酮-PGE 2和6-酮-PGF 1 α的水平显著降低。脂肪细胞在去甲肾上腺素诱导的脂解过程中产生大量的PGE 2和PGI 2。DKA是高儿茶酚胺和低胰岛素水平的典型情况，正是加速脂肪分解和脂肪细胞产生最大PGE 2和PGI 2所需的情况。脂肪细胞可能是DKA大鼠中存在的高血浆PGE 2和PGI 2衍生物水平以及DM动物中存在的PGI 2衍生物水平升高的重要来源。胰岛素和5-甲基吡唑-3-羧酸降低13，14-二氢-15-酮-PGE 2和6-酮-PGF 1 α水平的能力支持这一观点。DKA中PGE 2、PGI 2和TXA 2衍生物的高血浆水平以及DM中PGI 2衍生物的高血浆水平提高了所有三种母体化合物的高水平可能在DKA中循环以及高水平的PGI 2可能在DM中循环的可能性。两种结构上不相关的抗脂解剂抑制DKA中13，14-二氢-15-酮-PGE 2和6-酮-PGF 1 α水平升高，表明脂肪细胞可能是该疾病中两种衍生物血浆水平升高的主要来源。
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.
糖尿病中血小板血栓素合成增加。
DOI：
--
发表时间：
1981
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
Halushka,PV;Rogers,RC;Loadholt,CB;Colwell,JA
通讯作者：
Colwell,JA
过敏反应慢反应物质白三烯的放射免疫测定。
DOI：
10.1073/pnas.78.12.7692
发表时间：
1981
影响因子：
11.1
作者：
Levine,L;Morgan,RA;Lewis,RA;Austen,KF;Clark,DA;Marfat,A;Corey,EJ
通讯作者：
Corey,EJ