title: The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation.
abstract: We have previously shown that several gap junction uncouplers increase the uptake of glucose in astrocytes. The aim of the present work was to study whether the increase in glucose uptake was a consequence of the inhibition of gap junction communication and the purpose of this effect. Our results show that alpha-glycyrrhetinic acid and endothelin-1 increase the uptake of glucose in highly, but not in poorly, coupled astrocytes. This effect depended on connexin 43 levels and was abolished when the inhibition of gap junction communication was prevented by tolbutamide or ouabain. The inhibition of gap junctions increased the rate of glucose incorporation into DNA and RNA, which was inhibited by treatment with dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase, the regulatory enzyme of the pentose phosphate pathway. The inhibition of gap junctions significantly increased astrocyte proliferation, which was counteracted by tolbutamide. These effects were not observed in poorly coupled astrocytes expressing low levels of connexin 43. The increase in astrocyte proliferation caused by gap junction inhibition was prevented when either glucose uptake or the pentose phosphate pathway were inhibited. We conclude that the inhibition of gap junction communication induces astrocyte proliferation, resulting in an enhancement of glucose uptake and its utilization through the pentose phosphate pathway to provide ribose-5-phosphate for the synthesis of nucleic acids.
authors.affiliation: Unidad de Investigación, Hospital Universitario de Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Tabernero
authors.forename: C
authors.initials: C
authors.lastname: Jiménez
authors.forename: A
authors.initials: A
authors.lastname: Velasco
authors.forename: C
authors.initials: C
authors.lastname: Giaume
authors.forename: J M
authors.initials: JM
authors.lastname: Medina
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002450:Cell Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003561:Cytarabine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000737:chemistry / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010427:Pentose Phosphate Pathway / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012267:Ribosemonophosphates / Q000378:metabolism; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000964:Antimetabolites, Antineoplastic; D016895:Culture Media, Serum-Free; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D012267:Ribosemonophosphates; D003561:Cytarabine; D016718:Arachidonic Acid; D003571:Cytochalasin B; D003687:Dehydroepiandrosterone; C031626:ribose-5-phosphate; D010042:Ouabain; D014044:Tolbutamide; D005947:Glucose; D006034:Glycyrrhetinic Acid