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. ISSN 1015-8987

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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
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Engineering Faculty of Science > Life Sciences (2010- )
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
Date:	2012
Volume:	Vol.30
Number:	No.3
Page Range:	pp. 575-586
Identification Number:	10.1159/000341439
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Diabetes UK
Grant number:	09/0003913 (DUK)
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URI:	http://wrap.warwick.ac.uk/id/eprint/50057

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