title: Insulin receptor isoforms: an integrated view focused on gestational diabetes mellitus.
abstract: The human insulin receptor (IR) exists in two isoforms that differ by the absence (IR-A) or the presence (IR-B) of a 12-amino acid segment encoded by exon 11. Both isoforms are functionally distinct regarding their binding affinities and intracellular signalling. However, the underlying mechanisms related to their cellular functions in several tissues are only partially understood. In this review, we summarize the current knowledge in this field regarding the alternative splicing of IR isoform, tissue-specific distribution and signalling both in physiology and disease, with an emphasis on the human placenta in gestational diabetes mellitus (GDM). Furthermore, we discuss the clinical relevance of IR isoforms highlighted by findings that show altered insulin signalling due to differential IR-A and IR-B expression in human placental endothelium in GDM pregnancies. Future research and clinical studies focused on the role of IR isoform signalling might provide novel therapeutic targets for treating GDM to improve the adverse maternal and neonatal outcomes.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Advanced Centre for Chronic Diseases (ACCDiS), Faculty of Chemical & Pharmaceutical Sciences and Faculty of Medicine, Universidad de Chile, Santiago, Chile.|Faculty of Science, Universidad San Sebastián, Santiago, Chile.
authors.forename: F
authors.initials: F
authors.lastname: Westermeier
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|University Medical Centre Groningen (UMCG), Faculty of Medicine, University of Groningen, Groningen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Sáez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Arroyo
authors.affiliation: Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: F
authors.initials: F
authors.lastname: Toledo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Cellular Signalling and Differentiation Laboratory (CSDL), School of Medical Technology, Health Sciences Faculty, Universidad San Sebastian, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Sanhueza
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: F
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Leiva
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.|Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville, Spain.|University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Queensland, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D016640:Diabetes, Gestational / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D020033:Protein Isoforms; D011972:Receptor, Insulin
keywords: gestational diabetes; insulin receptor; placenta