title: Renal distal tubule proliferation and increased aquaporin 2 level but decreased urine osmolality in db/db mouse: treatment with chromium picolinate.
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.
authors: Department of Oral Biology, College of Dental Medicine, Georgia Health Sciences University, Augusta, GA 30912, USA. Mmozaffa@georgiahealth.edu
authors: Mahmood S
authors: MS
authors: Mozaffari
authors: Rafik
authors: R
authors: Abdelsayed
authors: Jun Yao
authors: JY
authors: Liu
authors: Ibrahim
authors: I
authors: Zakhary
authors: Babak
authors: B
authors: Baban
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000652:urine*; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003681:Dehydration / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D004195:Disease Models, Animal; D038321:Glycemic Index / Q000187:drug effects; D006029:Glycosuria; D007328:Insulin / Q000097:blood; D019394:Ki-67 Antigen / Q000032:analysis / Q000187:drug effects; D007686:Kidney Tubules, Distal / Q000473:pathology*; D008297:Male; D051379:Mice; D009994:Osmolar Concentration; D010848:Picolinic Acids / Q000008:administration & dosage*; D011141:Polyuria / Q000652:urine; D011897:Random Allocation
chemical_list: D051399:Aquaporin 2; D001786:Blood Glucose; D007328:Insulin; D019394:Ki-67 Antigen; D010848:Picolinic Acids; C030614:picolinic acid