Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

    1. Alessandra K Cardozo1
    1. 1ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), Brussels, Belgium
    2. 2Department of Cell and Developmental Biology, Universidade de São Paulo, São Paulo, Brazil
    3. 3Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
    1. Correspondence should be addressed to A K Cardozo; Email: akupperc{at}ulb.ac.be


    Insulin-secreting pancreatic β-cells are extremely dependent on their endoplasmic reticulum (ER) to cope with the oscillatory requirement of secreted insulin to maintain normoglycemia. Insulin translation and folding rely greatly on the unfolded protein response (UPR), an array of three main signaling pathways designed to maintain ER homeostasis and limit ER stress. However, prolonged or excessive UPR activation triggers alternative molecular pathways that can lead to β-cell dysfunction and apoptosis. An increasing number of studies suggest a role of these pro-apoptotic UPR pathways in the downfall of β-cells observed in diabetic patients. Particularly, the past few years highlighted a cross talk between the UPR and inflammation in the context of both type 1 (T1D) and type 2 diabetes (T2D). In this article, we describe the recent advances in research regarding the interplay between ER stress, the UPR, and inflammation in the context of β-cell apoptosis leading to diabetes.

    • Received 25 March 2016
    • Accepted 11 April 2016
    • Made available online as an Accepted Preprint 1 July 2016
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