| Calcium-Sensing Receptor Activation Increases Cell-Cell Adhesion and β-Cell Function. | |
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MedLine Citation:
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PMID: 22832156 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 [Ca(2+)](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. |
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Authors:
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Claire E Hills; Mustafa Y G Younis; Jeanette Bennett; Eleftherios Siamantouras; Kuo-Kang Liu; Paul E Squires |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-25 |
Journal Detail:
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Title: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Volume: 30 ISSN: 1421-9778 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9113221 Medline TA: Cell Physiol Biochem Country: - |
Other Details:
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Languages: ENG Pagination: 575-586 Citation Subset: - |
Copyright Information:
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Copyright © 2012 S. Karger AG, Basel. |
Affiliation:
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Schools of Life Sciences, University of Warwick, Coventry, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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