, Volume 57, Issue 8, pp 1517–1527 | Cite as

Impaired proteostasis: role in the pathogenesis of diabetes mellitus

  • Stéphane JaissonEmail author
  • Philippe Gillery


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.


Chaperones Diabetes mellitus Glycation Lysosome Proteasome Review 





Heat shock protein


Methionine sulfoxide reductase


Protein-l-isoaspartyl methyltransferase


Receptor for AGE


Small heat shock protein


Single-nucleotide polymorphism


Vascular endothelial growth factor receptor 2



The authors would like to thank E. van Schaftingen (de Duve Institute, Brussels, Belgium) for carefully reading the manuscript and providing constructive comments.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

Both authors were responsible for the conception and design of the manuscript, drafting the article and revising it critically for important intellectual content. Both authors approved the version to be published.


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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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