Diabetologia

, Volume 57, Issue 8, pp 1517–1527

Impaired proteostasis: role in the pathogenesis of diabetes mellitus

Review

DOI: 10.1007/s00125-014-3257-1

Cite this article as:
Jaisson, S. & Gillery, P. Diabetologia (2014) 57: 1517. doi:10.1007/s00125-014-3257-1

Abstract

In living organisms, proteins are regularly exposed to ‘molecular ageing’, which corresponds to a set of non-enzymatic modifications that progressively cause irreversible damage to proteins. This phenomenon is greatly amplified under pathological conditions, such as diabetes mellitus. For their survival and optimal functioning, cells have to maintain protein homeostasis, also called ‘proteostasis’. This process acts to maintain a high proportion of functional and undamaged proteins. Different mechanisms are involved in proteostasis, among them degradation systems (the main intracellular proteolytic systems being proteasome and lysosomes), folding systems (including molecular chaperones), and enzymatic mechanisms of protein repair. There is growing evidence that the disruption of proteostasis may constitute a determining event in pathophysiology. The aim of this review is to demonstrate how such a dysregulation may be involved in the pathogenesis of diabetes mellitus and in the onset of its long-term complications.

Keywords

Chaperones Diabetes mellitus Glycation Lysosome Proteasome Review 

Abbreviations

FN3K

Fructosamine-3-kinase

HSP

Heat shock protein

MSR

Methionine sulfoxide reductase

PIMT

Protein-l-isoaspartyl methyltransferase

RAGE

Receptor for AGE

sHSP

Small heat shock protein

SNP

Single-nucleotide polymorphism

VEGFR2

Vascular endothelial growth factor receptor 2

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Laboratory of Medical Biochemistry and Molecular BiologyUniversity of Reims Champagne ArdenneReimsFrance
  2. 2.CNRS UMR 7369, Extracellular Matrix and Cell DynamicsReimsFrance
  3. 3.Laboratory of Paediatric Biology and ResearchAmerican Memorial Hospital, University Hospital of ReimsReims CedexFrance

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