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Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases

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Gray, Elizabeth, Muller, Dany, Squires, Paul E., Asare-Anane, Henry, Huang, Guo-Cai, Amiel, Stephanie, Persaud, Shanta J. and Jones, Peter M.. (2006) Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases. JOURNAL OF ENDOCRINOLOGY, 190 (3). pp. 703-710. ISSN 0022-0795

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Official URL: http://dx.doi.org/10.1677/joe.1.06891

Abstract

The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca2+ homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR it physiological concentrations of extracellular Ca2+. CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was reduced by inhibitors of phospholipase C or calcium-calmodulin-dependent kinases, but not by a protein kinase C inhibitor. CaR activation was also associated with an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We suggest that the P-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between beta-cells.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Journal or Publication Title: JOURNAL OF ENDOCRINOLOGY
Publisher: SOC ENDOCRINOLOGY
ISSN: 0022-0795
Date: September 2006
Volume: 190
Number: 3
Number of Pages: 8
Page Range: pp. 703-710
Identification Number: 10.1677/joe.1.06891
Publication Status: Published
URI: http://wrap.warwick.ac.uk/id/eprint/32935

Data sourced from Thomson Reuters' Web of Knowledge

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