Renal distal tubule proliferation and increased aquaporin 2 level but decreased urine osmolality in db/db mouse: Treatment with chromium picolinate

Mahmood S. Mozaffari, Rafik Abdelsayed, Jun Yao Liu, Ibrahim Zakhary, Babak Baban

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)54-58
Number of pages5
JournalExperimental and Molecular Pathology
Volume92
Issue number1
DOIs
Publication statusPublished - Feb 1 2012

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Keywords

  • Aquaporin 2
  • Chromium picolinate
  • Diabetes
  • Glucosuria
  • Ki67
  • Kidney
  • Urine osmolality

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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