Article: article from journal or magazin.
Glucose represses connexin36 in insulin-secreting cells.
Journal of cell science
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
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.
Animals, Base Sequence, Cell Line, Tumor, Connexins, Cyclic AMP, Cyclic AMP Response Element Modulator, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Down-Regulation, Flavonoids, Forskolin, Glucose, Humans, Insulin-Secreting Cells, Isoquinolines, Mitogen-Activated Protein Kinases, Nifedipine, Promoter Regions, Genetic, RNA, Messenger, Rats, Response Elements, Sequence Deletion, Sulfonamides, Tetradecanoylphorbol Acetate
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