title: Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes.
abstract: Type 2 diabetes (T2D) is a complex metabolic disorder characterized by hyperglycemia in the context of insulin resistance, which precedes insulin deficiency as a result of β-cell failure. Accumulating evidence indicates that β-cell loss in T2D results as a response to the combination of oxidative stress and endoplasmic reticulum (ER) stress. Failure of the ER's adaptive capacity and further activation of the unfolded protein response may trigger macroautophagy (hereafter referred as autophagy) as a process of self-protection and inflammation. Many studies have shown that inflammation plays a very important role in the pathogenesis of T2D. Inflammatory mechanisms and cytokine production activated by stress via the inflammasome may further alter the normal structure of β-cells by inducing pancreatic islet cell apoptosis. Thus, the combination of oxidative and ER stress, together with autophagy insufficiency and inflammation, may contribute to β-cell death or dysfunction in T2D. Therapeutic approaches aimed at ameliorating stress and inflammation may therefore prove to be promising targets for the development of new diabetes treatment methods. Here, we discuss different mechanisms involved in stress and inflammation, and the role of antioxidants, endogenous and chemical chaperones, and autophagic pathways, which may shift the tendency from ER stress and apoptosis toward cell survival. Strategies targeting cell survival can be essential for relieving ER stress and reestablishing homeostasis, which may diminish inflammation and prevent pancreatic β-cell death associated with T2D.
authors: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Joel
authors: J
authors: Montane
authors: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Lisa
authors: L
authors: Cadavez
authors: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors: Anna
authors: A
authors: Novials
keywords: apoptosis; autophagy; chaperones; endoplasmic reticulum stress; inflammation; unfolded protein response