Acta Diabetologica

, Volume 49, Issue 6, pp 453–464

A discovery-phase urine proteomics investigation in type 1 diabetes

  • A. Soggiu
  • C. Piras
  • L. Bonizzi
  • H. A. Hussein
  • S. Pisanu
  • P. Roncada
Original Article

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.

Keywords

Type 1 diabetes Urine proteomics HbA1c Microalbuminuria Biomarkers Diabetic nephropathy 

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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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Soggiu
    • 1
  • C. Piras
    • 2
  • L. Bonizzi
    • 1
  • H. A. Hussein
    • 1
  • S. Pisanu
    • 3
  • P. Roncada
    • 4
  1. 1.Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Facoltà di Medicina VeterinariaUniversità Degli Studi di MilanoMilanItaly
  2. 2.Dipartimento di Scienze Zootecniche, Facoltà di AgrariaUniversità Degli Studi di SassariSassariItaly
  3. 3.Porto Conte Ricerche Srl, TramariglioAlgheroItaly
  4. 4.Istituto Sperimentale Italiano “L. Spallanzani”MilanItaly

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