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Renal 25‐hydroxycholecalciferol reabsorption is modulated in a type II diabetic rat model.
Author(s) -
Anderson Rachel L,
Rowling Matthew J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.731.6
Subject(s) - endocrinology , medicine , reabsorption , vitamin d and neurology , chemistry , kidney , type 2 diabetes , diabetes mellitus , proteinuria , renal physiology , vitamin , hormone
Alterations of serum levels of the major circulating form of vitamin D (25‐hydroxycholecalciferol, 25D 3 ) and its active hormone derivative (1,25‐dihydroxycholecalciferol, 1,25D 3 ) have long been associated with type II diabetes, although a mechanistic basis for this occurrence has not been fully elucidated. Renal reabsorption of vitamin D occurs by receptor‐mediated endocytosis of the 25D 3 ‐vitamin D binding protein (DBP) complex via megalin‐, cubilin‐, and disabled‐2 (Dab2)‐mediated endocytosis. Because renal dysfunction can lead to decreased expression of megalin and proteinuria , changes in serum vitamin D status in the uncontrolled diabetic may be due to increased urinary excretion of protein‐complexed 25D 3 . In the present study, we used a type II diabetic rat model [Zucker Diabetic Fatty Rats (ZDF)] to characterize the relationship between renal reuptake of 25D 3 ‐DBP and vitamin D homeostasis. Using immunoblotting and real‐time PCR, we analyzed transcript and protein levels of renal megalin, cubilin, and Dab2 and serum and urinary 25D 3 ,1,25D 3 and DBP levels in 16 wk old ZDF rats. Our preliminary data suggest that renal megalin and cubilin mRNA and protein expression is reduced in diabetic animals when compared to their lean non‐diabetic controls. In addition, preliminary results indicate that urinary excretion of DBP is markedly elevated in diabetic rats. Taken together, these data suggest that vitamin D status is compromised in diabetics due to poor vitamin D reabsorption in the kidney. Supported by USDA (Iowa State University Nutrition and Wellness Center SRPG to MR) and the Iowa State University Experiment Station.