title: Is Autophagy Altered in the Leukocytes of Type 2 Diabetic Patients?
abstract: It is unknown whether autophagy is altered in the leukocytes of type 2 diabetes (T2D) patients and whether oxidative and endoplasmic reticulum (ER) stresses regulate this mechanism. We studied anthropometric and metabolic parameters and evaluated oxidative stress, chromatin condensation, ER stress, and autophagy parameters in leukocytes of 103 T2D patients versus 109 sex- and age-matched controls. Patients showed increases in glucose, insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) compared with controls (p < 0.001). Leukocytes displayed enhanced total and mitochondrial reactive oxygen species (ROS), reduced mitochondrial mass, and increased chromatin condensation (p < 0.05). ER stress was also activated in diabetic patients, who displayed augmented glucose-regulated protein 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (P-eIF2α), and activating transcription factor 6 (ATF6) levels (p < 0.05). We also observed an increase in the autophagy markers, microtubule-associated protein light chain 3 (LC3)-II and Beclin 1 (p < 0.05), and significant positive correlations between Beclin 1 and total ROS (r = 0.667), GRP78 (r = 0.925) and P-eIF2α (r = 0.644), and between LC3-II and P-eIF2α (r = 0.636) and ATF6 (r = 0.601). Our results lead to the hypothesis that autophagy is activated in the leukocytes of T2D patients and that both oxidative and ER stress signaling pathways may be implicated in the induction of autophagy.
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .
authors.forename: Susana
authors.initials: S
authors.lastname: Rovira-Llopis
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Noelia
authors.initials: N
authors.lastname: Díaz-Morales
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Ana
authors.initials: A
authors.lastname: Blas-García
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Miriam
authors.initials: M
authors.lastname: Polo
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Sandra
authors.initials: S
authors.lastname: López-Domenech
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Ana
authors.initials: A
authors.lastname: Jover
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|4 Department of Medicine, University of Valencia , Valencia, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernández-Mijares
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .|5 Department of Physiology, University of Valencia , Valencia, Spain .
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Víctor
mesh_terms: D000368:Aged; D001343:Autophagy; D016022:Case-Control Studies; D053144:Cell Nucleus Shape; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species