Schmolke M, Schleicher E, Guder W G
Institut für Klinische Chemie, Krankenhaus München-Bogenhausen, Deutschland.
Eur J Clin Chem Clin Biochem. 1992 Oct;30(10):607-14. doi: 10.1515/cclm.1992.30.10.607.
The polyols, sorbitol and myo-inositol, seem to be involved in the development of diabetic complications of different organs. High concentrations of both polyols were found in kidney medulla in addition to trimethylamines. To investigate the influence of diabetes mellitus on the regulation of both polyols and glycerophosphorylcholine in kidney, these osmolytes were quantitated enzymatically along the corticopapillary axis in untreated, streptozotocin-diabetic and insulin-treated streptozotocin-diabetic rats. In control animals three individual osmolyte patterns were found: a steep gradient of sorbitol in the papilla, increasing amounts of glycerophosphorylcholine from the outer medulla to the papilla, and nearly equal amounts of myo-inositol in the renal medulla, decreasing towards the cortex. Diabetic rats exhibit an up to fourfold increase of inner medullary sorbitol, whereas myo-inositol was only elevated in the outer medulla. Glycerophosphorylcholine was lowered in the papillary tip and elevated in the outer medulla and cortex. Insulin treatment reduced sorbitol to a concentration between those of diabetic and control rats, caused a restoration of glycerophosphorylcholine in the papillary tip and outer medulla to control values, and increased cortical myo-inositol. These data confirm previous in vitro data, which show that papillary sorbitol specifically increases in hyperglycaemic states, thereby counteracting the increased extracellular tonicity due to elevated tissue glucose concentrations. Imbalance of extra- vs intracellular osmolality during insulin treatment may be involved in the pathomechanism of renal papillary necrosis.
多元醇、山梨醇和肌醇似乎与不同器官的糖尿病并发症的发展有关。除三甲胺外,在肾髓质中发现了高浓度的这两种多元醇。为了研究糖尿病对肾脏中多元醇和甘油磷酰胆碱调节的影响,在未治疗的、链脲佐菌素诱导糖尿病的和胰岛素治疗的链脲佐菌素诱导糖尿病的大鼠中,沿皮质 - 乳头轴对这些渗透溶质进行了酶定量分析。在对照动物中发现了三种不同的渗透溶质模式:乳头中山梨醇的陡峭梯度、从外髓到乳头甘油磷酰胆碱含量增加以及肾髓质中肌醇含量几乎相等,向皮质方向减少。糖尿病大鼠内髓中山梨醇增加了四倍之多,而肌醇仅在外髓中升高。甘油磷酰胆碱在乳头尖端降低,在外髓和皮质中升高。胰岛素治疗使山梨醇浓度降至糖尿病大鼠和对照大鼠之间,使乳头尖端和外髓中的甘油磷酰胆碱恢复到对照值,并增加了皮质中的肌醇。这些数据证实了先前的体外数据,即高血糖状态下乳头中山梨醇会特异性增加,从而抵消由于组织葡萄糖浓度升高导致的细胞外张力增加。胰岛素治疗期间细胞外与细胞内渗透压的失衡可能参与了肾乳头坏死的发病机制。