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Glucose-mediated spatial interactions of voltage dependent calcium channels and calcium sensing receptor in insulin producing beta-cells.

Authors: Parkash, J 
Citation: Parkash J Life Sci. 2011 Jan 31;88(5-6):257-64. doi: 10.1016/j.lfs.2010.12.002. Epub 2010 Dec 10.
Pubmed: (View Article at PubMed) PMID:21146545
DOI: Full-text: DOI:10.1016/j.lfs.2010.12.002

AIMS: The voltage dependent calcium channel (VDCC) e.g., L-type VDCC plays critical roles in the spatio-temporal regulation of intracellular calcium concentration ([Ca(2+)](i)) and insulin secretion by beta-cell. This study describes the involvement of 2.5 to 15mM glucose-induced spatial interactions between a calcium sensing receptor (CaR) and L-type VDCC in controlling Ca(2+) channel activity and insulin secretion in beta-cells in association with the nuclear translocation of a transcription factor nuclear factor kappa B (NF-kappaB). MAIN METHODS: The insulin producing beta-cells were exposed to 2.5, 5, 7.5, 10, and 15 mM glucose for 24 h at 37 degrees C. The confocal fluorescence imaging data was obtained by using antibodies against CaR and L-type VDCC. The nuclear translocation of NF-kappaB was measured by confocal fluorescence imaging using antibody against NF-kappaB. The insulin release was determined by enzyme-linked immunosorbent assay (ELISA). KEY FINDINGS: The confocal imaging data showed 6 to 12-fold enhancement in the colocalization correlation coefficient between CaR and VDCC in beta-cells exposed to glucose thereby indicating increased membrane delimited spatial interactions between these two membrane proteins. The confocal fluorescence imaging data showed that addition of glucose to beta-cells led to 1.8 to 2.7-fold increase in the nuclear translocation of NF-kappaB. The insulin ELISA data showed a significant increase in the 1st phase of glucose-induced insulin secretion in beta-cells exposed to increasing concentrations of glucose. SIGNIFICANCE: The results described in the present study further strengthen that VDCC and CaR can interact spatially to allow control over calcium channel activity and therefore glucose-induced insulin secretion by beta-cells.

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CRRD Object Information
CRRD ID: 7206831
Created: 2013-01-15
Species: All species
Last Modified: 2013-01-15
Status: ACTIVE



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