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链脲佐菌素诱导的糖尿病中肾小管哇巴因敏感性ATP酶增强

Enhanced renal tubular ouabain-sensitive ATPase in streptozotocin diabetes mellitus.

作者信息

Wald H, Scherzer P, Popovtzer M M

出版信息

Am J Physiol. 1986 Jul;251(1 Pt 2):F164-70. doi: 10.1152/ajprenal.1986.251.1.F164.

Abstract

The effect of streptozotocin-induced diabetes mellitus on rat renal ouabain-sensitive ATPase in six distinct nephron segments was studied. Twenty-four hours after administration of streptozotocin, blood glucose increased threefold (P less than 0.001), and glucosuria was evident. Aldosterone levels increased almost twofold (P less than 0.001). Ouabain-sensitive ATPase increased in the proximal segments PC (proximal convoluted tubule) and PS (proximal straight tubule) by 43 and 62%, respectively, (P less than 0.001) and CD (cortical collecting duct) ouabain-sensitive ATPase increased 77% (P less than 0.001). Ouabain-sensitive ATPase in the cortical (CTAL) and medullary (MTAL) thick ascending limbs of Henle's loop and in the DC (distal convoluted tubule) remained unchanged after 24 h of streptozotocin administration. Eight days after streptozotocin administration, when glomerular filtration rate (GFR) was already markedly elevated, ouabain-sensitive ATPase remained increased in the PC, PS, and CD but was significantly less compared with the activity after 24 h (P less than 0.05), whereas in the CTAL and MTAL a marked increase in ouabain-sensitive ATPase occurred by 54% in the CTAL and 65% in the MTAL (P less than 0.001). Aldosterone levels remained elevated compared with control but less than after 24 h. Pretreatment with deoxycorticosterone acetate abolished the increase in ouabain-sensitive ATPase in the CD. These findings show that streptozotocin-induced diabetes mellitus in the rat is associated with a substantial increase in ouabain-sensitive ATPase activity along most of the nephron. This increase in enzyme activity may represent a mechanism of physiological adaptation of the nephron to maintain electrolyte homeostasis in diabetes in face of the increased GFR and osmotic diuresis.

摘要

研究了链脲佐菌素诱导的糖尿病对大鼠六个不同肾单位节段哇巴因敏感ATP酶的影响。给予链脲佐菌素24小时后,血糖升高了两倍(P<0.001),且出现明显的糖尿。醛固酮水平几乎升高了一倍(P<0.001)。近端节段PC(近端曲管)和PS(近端直小管)中的哇巴因敏感ATP酶分别增加了43%和62%(P<0.001),皮质集合管(CD)的哇巴因敏感ATP酶增加了77%(P<0.001)。给予链脲佐菌素24小时后,亨氏袢皮质(CTAL)和髓质(MTAL)厚升支以及远端曲管(DC)中的哇巴因敏感ATP酶保持不变。给予链脲佐菌素8天后,当肾小球滤过率(GFR)已经显著升高时,PC、PS和CD中的哇巴因敏感ATP酶仍然升高,但与24小时后的活性相比显著降低(P<0.05),而在CTAL和MTAL中,哇巴因敏感ATP酶显著增加,CTAL增加了54%,MTAL增加了65%(P<0.001)。与对照组相比,醛固酮水平仍然升高,但低于24小时后。用醋酸脱氧皮质酮预处理可消除CD中哇巴因敏感ATP酶的增加。这些发现表明,大鼠中链脲佐菌素诱导的糖尿病与大多数肾单位中哇巴因敏感ATP酶活性的大幅增加有关。酶活性的这种增加可能代表肾单位的一种生理适应机制,以在糖尿病中面对增加的GFR和渗透性利尿时维持电解质稳态。

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