title: Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion.
abstract: Hypothalamic glucose detection participates in maintaining glycemic balance, food intake, and thermogenesis. Although hypothalamic neurons are the executive cells involved in these responses, there is increasing evidence that astrocytes participate in glucose sensing (GS); however, it is unknown whether astroglial networking is required for glucose sensitivity. Astroglial connexins 30 and 43 (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions, allowing for the intercellular transfer of small molecules such as glucose throughout the astroglial networks. Here, we hypothesized that hypothalamic glucose sensitivity requires these connexins. First, we showed that both Cxs are enriched in the rat hypothalamus, with highly concentrated Cx43 expression around blood vessels of the mediobasal hypothalamus (MBH). Both fasting and high glycemic levels rapidly altered the protein levels of MBH astroglial connexins, suggesting cross talk within the MBH between glycemic status and the connexins' ability to dispatch glucose. Finally, the inhibition of MBH Cx43 (by transient RNA interference) attenuated hypothalamic glucose sensitivity in rats, which was demonstrated by a pronounced decreased insulin secretion in response to a brain glucose challenge. These results illustrate that astroglial connexins contribute to hypothalamic GS.
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Allard
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Carneiro
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grall
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Cline
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Chrétien
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Baba-Aissa
authors.affiliation: 1] Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, Paris, France [2] University Pierre et Marie Curie, ED, N 158, Paris, France [3] MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.affiliation: 1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C580592:Gja1 protein, rat; C508770:Gjb6 protein, rat; D007328:Insulin; D009419:Nerve Tissue Proteins; D005947:Glucose