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A discovery-phase urine proteomics investigation in type 1 diabetes

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Abstract

Diabetes is a chronic metabolic disease which can lead to serious health problems particularly in and to the development of cardiovascular and renal complications. The aim of this study is to possibly identify distinctive molecular features in urine samples which might correlate to the progression and complications of type 1 diabetes. Diabetic patients with normo- and micro-albuminuria have been analyzed and compared to a group of control subjects. Urine proteins of control and type 1 diabetes subjects were investigated in their proteome profiles, using high-resolution two-dimensional gel electrophoresis separation and protein identifications by MALDI–TOF–MS and LC–MS/MS analysis. Proteomics analysis highlighted differential expression of several proteins between control and type 1 diabetes subjects. In particular, five proteins were found to be down-regulated and four proteins up-regulated. Lower protein representations in diabetic subjects were associated with Tamm–Horsfall urinary glycoprotein, apolipoprotein A-I, apolipoprotein E, α2-thiol proteinase inhibitor, and human complement regulatory protein CD59, while higher protein representations were found for α-1-microglobulin, zinc-α2 glycoprotein, α-1B glycoprotein, and retinol-binding protein 4. These differences were maintained comparing control subjects with type 1 diabetes normo-albuminuric and micro-albuminuric subjects. Furthermore, these proteins are correlated to glycosylated hemoglobin and microalbuminuria, confirming their role in diabetic pathology. This study gives new insights on potential molecular mechanisms associated with the complications of type 1 diabetic disease providing evidences of urine proteins potentially exploitable as putative prognostic biomarkers.

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Abbreviations

THP:

Tamm–Horsfall urinary glycoprotein

Apo A-1:

Apolipoprotein A-I

Apo E:

Apolipoprotein E

HMWK:

Kininogen-1 or α2-thiol proteinase inhibitor

CD59:

Human complement regulatory protein CD59

AMBP:

α-1-Microglobulin

ZA2G:

Zinc-α2 glycoprotein

A1BG:

α-1B Glycoprotein

RBP4:

Plasma retinol-binding protein

HbA1c :

Glycosylated hemoglobin

IDDM:

Insulin-dependent diabetes mellitus

NIDDM:

Non-insulin-dependent diabetes mellitus

MALDI–TOF:

Matrix-assisted laser desorption ionization–time of flight

LC–MS/MS:

Liquid chromatography tandem mass spectrometry

DN:

Diabetes nephropathy

T1D:

Type 1 diabetes

2-DE:

Two-dimensional electrophoresis

T2D:

Type 2 diabetes

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Acknowledgments

We wish to thank Prof. Francesco Cucca, Prof. Mario Maioli, for help in collecting the Sardinian type 1 diabetes families and for clinical information. This work was supported by project “ICT SIAI 101 SARDEGEN” (Proteotech srl).

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Authors and Affiliations

  1. Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Facoltà di Medicina Veterinaria, Università Degli Studi di Milano, Milan, Italy

    A. Soggiu, L. Bonizzi & H. A. Hussein

  2. Dipartimento di Scienze Zootecniche, Facoltà di Agraria, Università Degli Studi di Sassari, Sassari, Italy

    C. Piras

  3. Porto Conte Ricerche Srl, Tramariglio, Alghero, SS, Italy

    S. Pisanu

  4. Istituto Sperimentale Italiano “L. Spallanzani”, Milan, Italy

    P. Roncada

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  1. A. Soggiu
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  2. C. Piras
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Correspondence to P. Roncada.

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Communicated by Antonio Secchi.

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Soggiu, A., Piras, C., Bonizzi, L. et al. A discovery-phase urine proteomics investigation in type 1 diabetes. Acta Diabetol 49, 453–464 (2012). https://doi.org/10.1007/s00592-012-0407-0

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