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Calcium-sensing receptor activation increases cell-cell adhesion and ß-cell function
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Hills, Claire E., Younis, Mustafa Y. G., Bennett, Jeanette, Siamantouras, Eleftherios, Liu, Kuo-Kang and Squires, Paul E. (2012) Calcium-sensing receptor activation increases cell-cell adhesion and ß-cell function. Cellular Physiology and Biochemistry, Vol.30 (No.3). pp. 575-586. doi:10.1159/000341439 ISSN 1015-8987.
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WRAP_Hills_120912-2012ms125_-_accepted_version.pdf - Accepted Version Download (624Kb) | Preview |
Official URL: http://dx.doi.org/10.1159/000341439
Abstract
Background/Aims: The extracellular calcium-sensing receptor (CaR) is expressed in pancreatic β-cells where it is thought to facilitate cell-to-cell communication and augment insulin secretion. However, it is unknown how CaR activation improves β-cell function. Methods: Immunocytochemistry and western blotting confirmed the expression of CaR in MIN6 β-cell line. The calcimimetic R568 (1µM) was used to increase the affinity of the CaR and specifically activate the receptor at a physiologically appropriate extracellular calcium concentration. Incorporation of 5-bromo-2’-deoxyuridine (BrdU) was used to measure cell proliferation, whilst changes in non-nutrient-evoked cytosolic calcium were assessed using fura-2-microfluorimetry. AFM-single-cell-force spectroscopy related CaR-evoked changes in epithelial (E)-cadherin expression to improved functional tethering between coupled cells. Results: Activation of the CaR over 48hr doubled the expression of E-cadherin (206±41%) and increased L-type voltage-dependent calcium channel expression by 70% compared to control. These changes produced a 30% increase in cell-cell tethering and elevated the basal-to-peak amplitude of ATP (50µM) and tolbutamide (100µM)-evoked changes in cytosolic calcium. Activation of the receptor also increased PD98059 (1-100µM) and SU1498 (1-100µM)-dependent β-cell proliferation. Conclusion: Our data suggest that activation of the CaR increases E-cadherin mediated functional tethering between β-cells and increases expression of L-type VDCC and secretagogue-evoked changes in [Ca2+]i. These findings could explain how local changes in calcium, co-released with insulin, activate the CaR on neighbouring cells to help ensure efficient and appropriate secretory function.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QP Physiology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
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Library of Congress Subject Headings (LCSH): | Pancreatic beta cells -- Physiology, Calcium in the body, Cell adhesion | ||||
Journal or Publication Title: | Cellular Physiology and Biochemistry | ||||
Publisher: | Karger | ||||
ISSN: | 1015-8987 | ||||
Official Date: | 2012 | ||||
Dates: |
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Volume: | Vol.30 | ||||
Number: | No.3 | ||||
Page Range: | pp. 575-586 | ||||
DOI: | 10.1159/000341439 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 22 December 2015 | ||||
Date of first compliant Open Access: | 22 December 2015 | ||||
Funder: | Diabetes UK | ||||
Grant number: | 09/0003913 (DUK) |
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