Renal distal tubule proliferation and increased aquaporin 2 level but decreased urine osmolality in db/db mouse: Treatment with chromium picolinate
- 作者：Mahmood S. Mozaffari ; Mmozaffa@georgiahealth.edu ; Rafik Abdelsayed ; Jun Yao Liu ; Ibrahim Zakhary ; Babak Baban
- 关键词：Diabetes ; Kidney ; Glucosuria ; Aquaporin 2 ; Ki67 ; Urine osmolality ; Chromium picolinate
- 刊名：Experimental and Molecular Pathology
- 出版年：2012
- 期刊代码：291_00144800
- 类别：med
- 出版时间：February, 2012
- 卷：92
- 期：1
- 页码：54-58
- 文件大小：1139 K
摘要
Hallmark features of type 2 diabetes mellitus include glucosuria and polyuria. Further, renal aquaporin 2 is pivotal to regulation of fluid excretion and urine osmolality. Accordingly, we tested the hypothesis that the db/db mouse displays increased glucosuria and fluid excretion but reduced urine osmolality in association with decreased renal aquaporin 2 level. In addition, we examined the effect of chromium picolinate (Cr(pic)3) which is purported to improve glycemic control. The db/db mice excreted more urine in association with marked glucose excretion but lower urine osmolality than db/m control group. Light microscopic examination of renal tissue revealed proliferation of tubular structures in db/db compared to the db/m mice, a feature validated with Ki67 immunostaining. Further, these tubules showed generally similar immunostaining intensity and pattern for aquaporin 2 indicating that proliferated tubules are of distal origin. On the other hand, renal aquaporin 2 protein level was significantly higher in the db/db than db/m group. Treatment of db/db mice with Cr(pic)3 reduced plasma glucose and hemoglobin A1c (~ 15-17%, p < 0.05) and Ki67 positive cells but other parameters were similar to their untreated counterparts. Collectively, these findings suggest that proliferation of renal distal tubules and increased aquaporin 2 level likely represent an adaptive mechanism to regulate fluid excretion to prevent dehydration in the setting of marked glucosuria in the db/db mouse, features not affected by Cr(pic)3 treatment. These observations are of relevance to increasing interest in developing therapeutic agents that facilitate renal glucose elimination.