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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, Volume 190 (Number 3). pp. 703-710. doi:10.1677/joe.1.06891 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 | ||||
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Subjects: | R Medicine > RC Internal medicine | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Journal of Endocrinology | ||||
Publisher: | Society for Endocrinology | ||||
ISSN: | 0022-0795 | ||||
Official Date: | September 2006 | ||||
Dates: |
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Volume: | Volume 190 | ||||
Number: | Number 3 | ||||
Number of Pages: | 8 | ||||
Page Range: | pp. 703-710 | ||||
DOI: | 10.1677/joe.1.06891 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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