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


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.
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA. thrailkillkathrynm@uams.edu
Kathryn M
KM
Thrailkill
Teresa
T
Nimmo
R Clay
RC
Bunn
Gael E
GE
Cockrell
Cynthia S
CS
Moreau
Samuel
S
Mackintosh
Ricky D
RD
Edmondson
John L
JL
Fowlkes
D048868:Adaptor Proteins, Signal Transducing / Q000652:urine*; D000419:Albuminuria / Q000453:epidemiology / Q000209:etiology* / Q000652:urine; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D008297:Male; D040901:Proteomics / Q000379:methods; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012016:Reference Values
D048868:Adaptor Proteins, Signal Transducing; C476844:LRP2BP protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor