LOCALIZATION AND REGULATION OF RENAL NA+ MYO-INOSITOL COTRANSPORTER IN DIABETIC RATS/

We have examined the effect of diabetes on sodium/myo-inositol cotrans porter (SMIT) mRNA levels and myo-inositol content in the kidney to te st the hypothesis that diabetes-induced changes in renal myo-inositol levels are due to the regulation of SMIT mRNA levels. In streptozotoci n-induced diabetic rats, after 3, 7 and 28 days of diabetes, SMIT mRNA levels in tile whole kidney were increased three- to fivefold, and re mained increased by about twofold after six months of diabetes. Insuli n treatment of diabetic rats normalized blood glucose levels and preve nted the increase in SMIT mRNA levels. Treating diabetic rats with sor binil, an aldose reductase inhibitor, corrected the abnormal accumulat ion of sorbitol but had no effect on the diabetes-induced increase in renal SMIT mRNA levels. The regional distribution of SMIT mRNA from no rmal rats showed a relative abundance in cortex, outer medulla, and in ner medulla of 1.0:3.4:7.0. After seven daps of diabetes, the levels o f SMIT mRNA and myo-inositol content were significantly increased only in the outer medulla. In situ hybridization studies revealed that SMI T mRNA in the outer medulla was predominately localized to the medulla ry thick ascending limbs of Henle's loop and was not localized to any specific cell in the inner medulla. This distribution pattern was unch anged in diabetic rats. These studies show that diabetes causes an inc rease in renal SMIT mRNA, which is primarily localized to the outer me dulla. Accumulation of myo-inositol by tile thick ascending limb of He nle's loop may account for most of the increase caused by diabetes.