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

• Published in: Diabetes care Vol. 32; no. 7; pp. 1266 - 1268
• Main Authors: Thrailkill, Kathryn M, Nimmo, Teresa, Bunn, R. Clay, Cockrell, Gael E, Moreau, Cynthia S, Mackintosh, Samuel, Edmondson, Ricky D, Fowlkes, John L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2009
• Subjects: Adaptor Proteins, Signal Transducing - urine; Albuminuria; Albuminuria - epidemiology; Albuminuria - etiology; Albuminuria - urine; Biological and medical sciences; Blood Pressure; Cells; Complications and side effects; Diabetes; Diabetes Mellitus, Type 1 - urine; Diabetes. Impaired glucose tolerance; Diabetic nephropathies; Diabetic Nephropathies - urine; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glomerular Filtration Rate; Humans; Kidneys; Low Density Lipoprotein Receptor-Related Protein-2; Male; Medical sciences; Metabolic diseases; Miscellaneous; Neurons; Original Research; Proteins; Proteomics - methods; Public health. Hygiene; Public health. Hygiene-occupational medicine; Receptors, Cell Surface - metabolism; Reference Values; Risk factors; Studies; Type 1 diabetes; United States; Endocrinopathy; Human; Immunopathology; Excretion; Urinary system disease; Nutrition; Cubilin; Albumin; Autoimmune disease; Metabolic diseases; Endocytosis; Association; Type 1 diabetes; Endocrinology; Microalbuminuria; Proteinuria; Biological receptor
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc09-0112

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.