Possible participation of an islet B-Cell calcium-sensing receptor in insulin release

The calcium-sensing receptor gene was recently shown to be expressed in rat pancreatic islets and purified islet B-cells. In this study, we investigat ed the possible role of this receptor in the regulation of insulin release from isolated rat pancreatic islets. Poly-L-arginine (0.2-0.3 mu M) and pol y-L-lysine (0.03-0.1 mu M) increased insulin output evoked by D-glucose (8. 3 mM), This positive effect faded out at higher concentrations of the basic peptides. Likewise, the release of insulin evoked by 8.3 mM D-glucose was significantly lower at high (1.0 mM) than low (0.05-0.1 mM) concentrations of neomycin, The insulinotropic action of Ba2+ in Ca2+-deprived islets was potentiated in rats pretreated with pertussis toxin, However, Gd3+ inhibite d insulin release evoked by D-glucose in islets prepared from normal rats o r animals pretreated with pertussis toxin and incubated in the absence or p resence of either theophylline or forskolin, Gd3+ (0.3 mM) failed to affect effluent radioactivity from islets prelabeled with myo-[2-H-3]inositol and cyclic AMP net production in islets incubated in the absence or presence o f forskolin, Gd3+ decreased, however, Ca-45 efflux from prelabeled islets p erifused in the absence or presence of extracellular Ca2+. It is speculated that a negative insulinotropic action mediated by the calcium-sensing rece ptor, and possibly attributable to a fall in cytosolic Ca2+ concentration, may prevent excessive insulin secretion in pathological situations of hyper calcemia.