title: Metabolism Regulates Exposure of Pancreatic Islets to Circulating Molecules In Vivo.
abstract: Pancreatic β-cells modulate insulin secretion through rapid sensing of blood glucose and integration of gut-derived signals. Increased insulin demand during pregnancy and obesity alters islet function and mass and leads to gestational diabetes mellitus and type 2 diabetes in predisposed individuals. However, it is unclear how blood-borne factors dynamically access the islets of Langerhans. Thus, understanding the changes in circulating molecule distribution that accompany compensatory β-cell expansion may be key to developing novel antidiabetic therapies. Here, using two-photon microscopy in vivo in mice, we demonstrate that islets are almost instantly exposed to peaks of circulating molecules, which rapidly pervade the tissue before clearance. In addition, both gestation and short-term high-fat-diet feeding decrease molecule extravasation and uptake rates in vivo in islets, independently of β-cell expansion or islet blood flow velocity. Together, these data support a role for islet vascular permeability in shaping β-cell adaptive responses to metabolic demand by modulating the access and sensing of circulating molecules.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Michau
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France Section of Cell Biology and Functional Genomics, Department of Medicine, Imperial College London, Imperial Centre for Translational and Experimental Medicine, Hammersmith Hospital, London, U.K. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, U.K.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hodson
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontanaud
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Guillou
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France Lymphocyte Differentiation, Tolerance, and Metabolism Laboratory, Institute for Regenerative Medicine and Biotherapy, U1183, Montpellier, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Espinosa-Carrasco
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France Charles Coulomb Laboratory, University of Montpellier, CNRS, UMR-5221, Montpellier, France.
authors.forename: François
authors.initials: F
authors.lastname: Molino
authors.affiliation: Division of Molecular Neuroendocrinology, National Institute for Medical Research, London, U.K.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Peters
authors.affiliation: Division of Molecular Neuroendocrinology, National Institute for Medical Research, London, U.K.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Robinson
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Le Tissier
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France INSERM, U1191, Montpellier, France University of Montpellier, Montpellier, France marie.schaeffer@igf.cnrs.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaeffer
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002199:Capillary Permeability; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D016640:Diabetes, Gestational / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000069416:Intravital Microscopy; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D010179:Pancreas / Q000098:blood supply; D011247:Pregnancy
chemical_list: D007328:Insulin