title: Junctional communication of pancreatic beta cells contributes to the control of insulin secretion and glucose tolerance.
abstract: Proper insulin secretion requires the coordinated functioning of the numerous beta cells that form pancreatic islets. This coordination depends on a network of communication mechanisms whereby beta cells interact with extracellular signals and adjacent cells via connexin channels. To assess whether connexin-dependent communication plays a role in vivo, we have developed transgenic mice in which connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is expressed in beta cells. We show that the altered beta-cell coupling that results from this expression causes reduced insulin secretion in response to physiologically relevant concentrations of glucose and abnormal tolerance to the sugar. These alterations were observed in spite of normal numbers of islets, increased insulin content, and preserved secretory response to glucose by individual beta cells. Moreover, glucose-stimulated islets showed improved electrical synchronization of these cells and increased cytosolic levels of Ca(2+). The results show that connexins contribute to the control of beta cells in vivo and that their excess is detrimental for insulin secretion.
authors.affiliation: Department of Morphology, and. Department of Medicine, University of Geneva, Medical School, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Charollais
authors.forename: A
authors.initials: A
authors.lastname: Gjinovci
authors.forename: J
authors.initials: J
authors.lastname: Huarte
authors.forename: J
authors.initials: J
authors.lastname: Bauquis
authors.forename: A
authors.initials: A
authors.lastname: Nadal
authors.forename: F
authors.initials: F
authors.lastname: Martín
authors.forename: E
authors.initials: E
authors.lastname: Andreu
authors.forename: J V
authors.initials: JV
authors.lastname: Sánchez-Andrés
authors.forename: A
authors.initials: A
authors.lastname: Calabrese
authors.forename: D
authors.initials: D
authors.lastname: Bosco
authors.forename: B
authors.initials: B
authors.lastname: Soria
authors.forename: C B
authors.initials: CB
authors.lastname: Wollheim
authors.forename: P L
authors.initials: PL
authors.lastname: Herrera
authors.forename: P
authors.initials: P
authors.lastname: Meda
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002450:Cell Communication; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007365:Intercellular Junctions / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D005947:Glucose; D007328:Insulin; D000097002:Gap Junction beta-1 Protein