title: Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and β-Cell Dysfunction.
abstract: The prevalence of diabetes mellitus (DM) is increasing worldwide, a consequence of the alarming rise in obesity and metabolic syndrome (MetS). Oxidative stress and inflammation are key physiological and pathological events linking obesity, insulin resistance, and the progression of type 2 DM (T2DM). Unresolved inflammation alongside a "glucolipotoxic" environment of the pancreatic islets, in insulin resistant pathologies, enhances the infiltration of immune cells which through secretory activity cause dysfunction of insulin-secreting β-cells and ultimately cell death. Recent molecular investigations have revealed that mechanisms responsible for insulin resistance associated with T2DM are detected in conditions such as obesity and MetS, including impaired insulin receptor (IR) signalling in insulin responsive tissues, oxidative stress, and endoplasmic reticulum (ER) stress. The aim of the present review is to describe the evidence linking oxidative stress and inflammation with impairment of insulin secretion and action, which result in the progression of T2DM and other conditions associated with metabolic dysregulation.
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, 6102 Perth, WA, Australia.
authors.forename: Kevin Noel
authors.initials: KN
authors.lastname: Keane
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, 6102 Perth, WA, Australia ; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Vinicius Fernandes
authors.initials: VF
authors.lastname: Cruzat
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, 6102 Perth, WA, Australia ; Post-Graduate Program in Medical Sciences: Endocrinology, Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carlessi
authors.affiliation: Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Paulo Ivo Homem
authors.initials: PI
authors.lastname: de Bittencourt
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, 6102 Perth, WA, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Newsholme
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007328:Insulin; D017382:Reactive Oxygen Species