Glucose represses connexin36 in insulin-secreting cells
Open Access
- 15 November 2005
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 118 (22), 5335-5344
- https://doi.org/10.1242/jcs.02600
Abstract
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 β-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 Ca2+-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.Keywords
This publication has 50 references indexed in Scilit:
- Regulation of ERK1 and ERK2 by Glucose and Peptide Hormones in Pancreatic β CellsOnline Journal of Public Health Informatics, 2003
- Lentivirus-mediated transduction of connexin cDNAs shows level- and isoform-specific alterations in insulin secretion of primary pancreaticβ-cellsJournal of Cell Science, 2003
- Differential Activation Mechanisms of Erk-1/2 and p70S6K by Glucose in Pancreatic β-CellsDiabetes, 2003
- Connexin 36 Controls Synchronization of Ca2+ Oscillations and Insulin Secretion in MIN6 CellsDiabetes, 2003
- Exendin-4 as a Stimulator of Rat Insulin I Gene Promoter Activity via bZIP/CRE Interactions Sensitive to Serine/Threonine Protein Kinase Inhibitor Ro 31-8220Endocrinology, 2002
- The Transcriptional Repressor REST Determines the Cell-Specific Expression of the Human MAPK8IP1 Gene Encoding IB1 (JIP-1)Molecular and Cellular Biology, 2001
- Structure, chromosomal localization, and brain expression of human Cx36 geneJournal of Neuroscience Research, 1999
- Multiple protein kinase A-regulated events are required for transcriptional induction by cAMP.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Glucose regulates acetyl-CoA carboxylase gene expression in a pancreatic beta-cell line (INS-1).Online Journal of Public Health Informatics, 1993
- Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines.Endocrinology, 1992