<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Allagnat F</dc:creator>
  <dc:creator>Martin D</dc:creator>
  <dc:creator>Condorelli DF</dc:creator>
  <dc:creator>Waeber G</dc:creator>
  <dc:creator>Haefliger JA</dc:creator>
  <dc:date>2005</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">The gap-junction protein connexin36 (Cx36) contributes to control the functions of insulin-producing cells. In this study, we investigated whether the expression of Cx36 is regulated by glucose in insulin-producing cells. Glucose caused a significant reduction of Cx36 in insulin-secreting cell lines and freshly isolated pancreatic rat islets. This decrease appeared at the mRNA and the protein levels in a dose- and time-dependent manner. 2-Deoxyglucose partially reproduced the effect of glucose, whereas glucosamine, 3-O-methyl-D-glucose and leucine were ineffective. Moreover, KCl-induced depolarization of beta-cells had no effect on Cx36 expression, indicating that glucose metabolism and ATP production are not mandatory for glucose-induced Cx36 downregulation. Forskolin mimicked the repression of Cx36 by glucose. Glucose or forskolin effects on Cx36 expression were not suppressed by the L-type Ca(2+)-channel blocker nifedipine but were fully blunted by the cAMP-dependent protein kinase (PKA) inhibitor H89. A 4 kb fragment of the human Cx36 promoter was identified and sequenced. Reporter-gene activity driven by various Cx36 promoter fragments indicated that Cx36 repression requires the presence of a highly conserved cAMP responsive element (CRE). Electrophoretic-mobility-shift assays revealed that, in the presence of a high glucose concentration, the binding activity of the repressor CRE-modulator 1 (CREM-1) is enhanced. Taken together, these data provide evidence that glucose represses the expression of Cx36 through the cAMP-PKA pathway, which activates a member of the CRE binding protein family.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://sonar.ch/global/documents/277986</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.02600</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/16263767</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:source>Journal of cell science. - 2005</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Animals</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Base Sequence</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Cell Line, Tumor</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Colforsin</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Connexins</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Cyclic AMP</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Cyclic AMP Response Element Modulator</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Cyclic AMP-Dependent Protein Kinases</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">DNA-Binding Proteins</dc:subject>
  <dc:subject xmlns:ns10="xml" ns10:lang="en">Down-Regulation</dc:subject>
  <dc:subject xmlns:ns11="xml" ns11:lang="en">Flavonoids</dc:subject>
  <dc:subject xmlns:ns12="xml" ns12:lang="en">Glucose</dc:subject>
  <dc:subject xmlns:ns13="xml" ns13:lang="en">Humans</dc:subject>
  <dc:subject xmlns:ns14="xml" ns14:lang="en">Insulin-Secreting Cells</dc:subject>
  <dc:subject xmlns:ns15="xml" ns15:lang="en">Isoquinolines</dc:subject>
  <dc:subject xmlns:ns16="xml" ns16:lang="en">Mitogen-Activated Protein Kinases</dc:subject>
  <dc:subject xmlns:ns17="xml" ns17:lang="en">Nifedipine</dc:subject>
  <dc:subject xmlns:ns18="xml" ns18:lang="en">Promoter Regions, Genetic</dc:subject>
  <dc:subject xmlns:ns19="xml" ns19:lang="en">RNA, Messenger</dc:subject>
  <dc:subject xmlns:ns20="xml" ns20:lang="en">Rats</dc:subject>
  <dc:subject xmlns:ns21="xml" ns21:lang="en">Response Elements</dc:subject>
  <dc:subject xmlns:ns22="xml" ns22:lang="en">Sequence Deletion</dc:subject>
  <dc:subject xmlns:ns23="xml" ns23:lang="en">Sulfonamides</dc:subject>
  <dc:subject xmlns:ns24="xml" ns24:lang="en">Tetradecanoylphorbol Acetate</dc:subject>
  <dc:title xmlns:ns25="xml" ns25:lang="en">Glucose represses connexin36 in insulin-secreting cells.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>