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    Diabetes Care. 2009 Jul;32(7):1266-8. Epub 2009 Apr 14.

    Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin.

    Thrailkill KM, Nimmo T, Bunn RC, Cockrell GE, Moreau CS, Mackintosh S, Edmondson RD, Fowlkes JL.

    Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA. thrailkillkathrynm@uams.edu

    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 and microalbuminuria that 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 nondiabetic individuals, 12 subjects with type 1 diabetes yet normal urinary albumin excretion rates, and 12 subjects with type 1 diabetes and microalbuminuria (type 1 diabetes + microalbuminuria). RESULTS: The abundance of megalin and cubilin, two multiligand receptors expressed in kidney proximal tubule cells and involved with the reuptake of filtered albumin and megalin/cubilin ligands, was significantly increased in type 1 diabetes + microalbuminuria urine, compared with both nonalbuminuric groups. CONCLUSIONS: Aberrant shedding of megalin and cubilin could contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.

    PMID: 19366958 [PubMed - indexed for MEDLINE]

    PMCID: 2699744

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