Dysregulation of the intrarenal vitamin D endocytic pathway in a nephropathy-prone mouse model of type 1 diabetes

John L. Fowlkes, R. Clay Bunn, Gael E. Cockrell, Lindsey M. Clark, Elizabeth C. Wahl, Charles K. Lumpkin, Kathryn M. Thrailkill

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Microalbuminuria in humans with Type 1 diabetes (T1D) is associated with increased urinary excretion of megalin, as well as many megalin ligands, including vitamin-D-binding protein (VDBP). We examined the DBA/2J diabetic mouse, nephropathy prone model, to determine if megalin and VDBP excretion coincide with the development of diabetic nephropathy. Megalin, VDBP, and 25-hydroxy-vitamin D (25-OHD) were measured in urine, and genes involved in vitamin D metabolism were assessed in renal tissues from diabetic and control mice at 10, 15, and 18 weeks following the onset of diabetes. Megalin, VDBP, and 25-OHD were increased in the urine of diabetic mice. 1- hydroxylase (CYP27B1) mRNA in the kidney was persistently increased in diabetic mice, as were several vitamin D-target genes. These studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intrarenal and extrarenal vitamin D deficiencies.

Original languageEnglish
Article number269378
JournalExperimental Diabetes Research
Volume2011
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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