title: Dysregulation of the intrarenal vitamin D endocytic pathway in a nephropathy-prone mouse model of type 1 diabetes.
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-α 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.
authors: Arkansas Children's Hospital Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, 1 Children's Way, Slot 512-6, Little Rock, AR 72202, USA. fowlkesjohnl@uams.edu
authors: John L
authors: JL
authors: Fowlkes
authors: R Clay
authors: RC
authors: Bunn
authors: Gael E
authors: GE
authors: Cockrell
authors: Lindsey M
authors: LM
authors: Clark
authors: Elizabeth C
authors: EC
authors: Wahl
authors: Charles K
authors: CK
authors: Lumpkin
authors: Kathryn M
authors: KM
authors: Thrailkill
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004705:Endocytosis / Q000502:physiology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000502:physiology; D013311:Streptozocin; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D014807:Vitamin D; D013311:Streptozocin