title: Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus.
abstract: Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.
authors.affiliation: a U.O.C. Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology , Department of Internal and Specialty Medicine , Azienda Ospedaliera Universitaria (AOU), Università degli Studi della Campania "Luigi Vanvitelli ," Italy.|b Department of Experimental Medicine , Second University of Naples , Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Sommese
authors.affiliation: c Department of Sciences and Technologies , University of Sannio , Benevento , Italy.|d CEINGE-Advanced Biotechnologies , Naples , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zullo
authors.affiliation: c Department of Sciences and Technologies , University of Sannio , Benevento , Italy.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Mancini
authors.affiliation: a U.O.C. Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology , Department of Internal and Specialty Medicine , Azienda Ospedaliera Universitaria (AOU), Università degli Studi della Campania "Luigi Vanvitelli ," Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Fabbricini
authors.affiliation: e IRCCS Research Institute SDN , Naples , Italy.|f Department of Studies of Institutions and Territorial Systems , University of Naples Parthenope , Naples , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soricelli
authors.affiliation: a U.O.C. Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology , Department of Internal and Specialty Medicine , Azienda Ospedaliera Universitaria (AOU), Università degli Studi della Campania "Luigi Vanvitelli ," Italy.|e IRCCS Research Institute SDN , Naples , Italy.|g Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences , Second University of Naples , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D064987:Cell- and Tissue-Based Therapy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D044127:Epigenesis, Genetic; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics; D053495:Osteopontin / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D057170:Translational Research, Biomedical
chemical_list: D016328:NF-kappa B; D051193:Toll-Like Receptors; D053495:Osteopontin
keywords: Bioinformatics; epigenetics; inflammation; transgenerational epigenetics; translational medicine; type 2 diabetes