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

Life Sci. 2011 Jan 31;88(5-6):257-64. doi: 10.1016/j.lfs.2010.12.002. Epub 2010 Dec 10.


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 β-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 β-cells in association with the nuclear translocation of a transcription factor nuclear factor kappa B (NF-κB).

Main methods: The insulin producing β-cells were exposed to 2.5, 5, 7.5, 10, and 15 mM glucose for 24 h at 37 °C. The confocal fluorescence imaging data was obtained by using antibodies against CaR and L-type VDCC. The nuclear translocation of NF-κB was measured by confocal fluorescence imaging using antibody against NF-κB. 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 β-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 β-cells led to 1.8 to 2.7-fold increase in the nuclear translocation of NF-κB. The insulin ELISA data showed a significant increase in the 1st phase of glucose-induced insulin secretion in β-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 β-cells.

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Cell Line
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Glucose / metabolism*
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / physiology*
  • Microscopy, Confocal
  • Rats
  • Receptors, Calcium-Sensing / metabolism*


  • Calcium Channels
  • Insulin
  • Receptors, Calcium-Sensing
  • Glucose