Details

Autor(en) / Beteiligte

• Gray, Elizabeth
• Muller, Dany
• Squires, Paul E
• Asare-Anane, Henry
• Huang, Guo-Cai
• Amiel, Stephanie
• Persaud, Shanta J
• Jones, Peter M

Titel

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

Ist Teil von

• Journal of endocrinology, 2006-09, Vol.190 (3), p.703-710

Ort / Verlag

Colchester: BioScientifica

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 at 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 β-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between β-cells.