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Microalbuminuria in Type 1 Diabetes Is Associated With Enhanced Excretion of the Endocytic Multiligand Receptors Megalin and Cubilin

Authors
Journal
Diabetes Care
0149-5992
Publisher
American Diabetes Association
Publication Date
Volume
32
Issue
7
Identifiers
DOI: 10.2337/dc09-0112
Keywords
  • Original Research
  • Pathophysiology/Complications
Disciplines
  • Biology
  • Medicine

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 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.

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