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

Gray, Elizabeth and Muller, Dany and Squires, Paul E. and Asare-Anane, Henry and Huang, Guo-Cai and Amiel, Stephanie and 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

Full content URL: http://dx.doi.org/10.1677/joe.1.06891

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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.

Additional Information:Made available online as an Accepted Preprint 17 July 2006
Keywords:Human islet, Endocrinology
Subjects:Library of Congress Subject Areas > R Medicine > RC Internal medicine
Divisions:College of Science > School of Life Sciences
ID Code:14081
Deposited On:20 Apr 2011 16:29

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