Microalbuminuria in type 1 diabetes mellitus is associated with enhanced excretion of the endocytic, multiligand receptors megalin and cubilin
- Kathryn M. Thrailkill, MD (thrailkillkathrynm{at}uams.edu)1,
- Teresa Nimmo, MD1,
- R. Clay Bunn, PhD1,
- Gael E. Cockrell1,
- Cynthia S. Moreau1,
- Samuel Mackintosh, PhD2,
- Ricky D. Edmondson, PhD3 and
- John L. Fowlkes, MD1
- Departments of Pediatrics1 and
- Biochemistry and Molecular Biology2, and the
- Myeloma Institute for Research and Therapy3, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock AR, USA 72205
Abstract
Objective - Proteinuria is the hallmark of diabetic nephropathy; yet glomerular histology does not fully explain mechanisms contributing to proteinuria. Our objective was to identify proteins in the urine of individuals with type 1 diabetes (T1DM) and microalbuminuria which might implicate a mechanistic pathway operative in proteinuria.
Research Design and Methods - Using a GeLC/MS platform proteomics approach, we compared the urine proteome from 12 healthy non-diabetic individuals, 12 subjects with T1DM yet normal urinary albumin excretion rates and 12 subjects with T1DM and microalbuminuria (T1DM + MA).
Results - The abundance of megalin and cubilin, two multiligand receptors expressed in kidney proximal tubule cells and involved with the re-uptake of filtered albumin and megalin/cubilin ligands, was significantly increased in T1DM + MA urine, compared to both non-albuminuric groups.
Conclusions - Aberrant shedding of megalin and cubilin could contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.
Footnotes
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- Received January 20, 2009.
- Accepted March 31, 2009.
- Copyright © American Diabetes Association
