title: Glibenclamide Prevents Diabetes in NOD Mice.
abstract: Previous work has revealed that Cx36, the sole connexin expressed in the insulin-producing beta cells, enhances the secretion of insulin, and promotes the resistance of beta cells against pro-inflammatory cytokines. In parallel, the anti-diabetic sulphonylurea glibenclamide was shown to promote the assembly and function of Cx36 channels. Here, we assessed whether glibenclamide could protect the insulin-producing cells against conditions mimicking those expected at the onset of type 1 diabetes. We found that the drug 1) protected in vitro the mouse MIN6 cells from the apoptosis and loss of Cx36, which are induced by Th1 cytokines; 2) prevented the development of hyperglycemia as well as the loss of beta cells and Cx36, which rapidly develop with aging in untreated NOD mice; 3) modified the proportion of effector CD4+ and CD8+ T cells in pancreatic draining lymph nodes. The data imply that an early glibenclamide treatment may help protecting beta cells against the autoimmune attack, which triggers the development of type 1 diabetes.
authors.affiliation: Departement of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Smaragda
authors.initials: S
authors.lastname: Lamprianou
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Leuven, Belgium.
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.affiliation: Departement of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Bou Saab
authors.affiliation: Departement of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Helena
authors.initials: H
authors.lastname: Pontes
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Departement of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007340:Insulinoma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D005905:Glyburide