International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2015.291.299ChuRuth GeYing YangMing 42015114KB-R7943, a Na+/Ca+ exchanger 1 (NCX1) inhibitor, was found to enhance Glucose-Stimulated Insulin Secretion (GSIS) from human and mouse pancreatic islets through inhibiting the forward mode of NCX1. This report studied the effects of KB-R7943 and a different NCX1 inhibitor SN-6, on GSIS from INS-1E cells, a rat pancreatic β-cell line and the potential mechanisms of action. It was found that KB-R7943 significantly enhanced GSIS from INS-1E cells in a concentration-dependent manner. In contrast, no significant effect was observed for SN-6 on GSIS. Similarly, KB-R7943 but not SN-6, enhanced glipizide, a sulfonylurea, stimulated insulin secretion from INS-1E cells. In addition, KB-R7943 but not SN-6, significantly enhanced glipizide-stimulated increase of intracellular Ca2+ ([Ca2+]i). Transient transfection with an NCX1 siRNA resulted in 70 and 62% knockdown of NCX1 gene and protein expression, respectively, in INS-1E cells. Surprisingly, knockdown of NCX1 had little impact on KB-R7943-induced enhancement of glucose- or glipizide-stimulated insulin secretion. Similarly knockdown of NCX1 did not affect KB-R7943 mediated enhancement of glipizide-stimulated increase of [Ca2+]i. Data suggest that the enhancement effect of KB-R7943 on GSIS in INS-1E cells most likely is mediated through an NCX1-independent pathway.]]>Amran, M.S., N. Homma and K. Hashimoto,2003+-Ca2+ exchange inhibitor.]]>21255276Annunziato, L., G. Pignataro and G.F. Di Renzo,2004+/Ca2+ exchanger: From molecular biology to therapeutic perspectives.]]>56633654Barrientos, G., D.D. Bose, W. Feng, I. Padilla and I.N. Pessah,2009+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy) phenyl) ethyl) isothiourea methanesulfonate (KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels.]]>76560568Bers, D.M., J.W.M. Bassani and R.A. Bassani,1996779430442Braun, M., R. Ramracheya, M. Bengtsson, Q. Zhang and J. Karanauskaite et al.,20085716181628Brustovetsky, T., M.K. Brittain, P.L. Sheets, T.R. Cummins, V. Pinelis and N. Brustovetsky,2011+/Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I.]]>162255270Cheng, H., Y. Zhang, C. Du, C.E. Dempsey and J.C. Hancox,201216522602273Dufer, M., Y. Neye, K. Horth, P. Krippeit-Drews and A. Hennige et al.,201154423432Elbashir, S.M., J. Harborth, W. Lendeckel, A. Yalcin, K. Weber and T. Tuschl,2001411494498Hamming, K.S.C., D. Soliman, N.J. Webster, G.J. Searle and L.C. Matemisz et al.,20105916861693Herchuelz, A., O. Diaz-Horta and F. van Eylen,2002976315324Herchuelz, A., A. Kamagate, H. Ximenes and F. van Eylen,20072+-ATPase in β cell function and death.]]>1099456467Herchuelz, A., E. Nguidjoe, L. Jiang and N. Pachera,2013+/Ca2+ exchange and the plasma membrane Ca2+-ATPase in β-cell function and diabetes.]]>961385394Iwamoto, T.,2004+/Ca2+ exchanger studies: Molecular pharmacology of Na+/Ca2+ exchange inhibitors.]]>962732Iwamoto, T., Y. Watanabe, S. Kita and M.P. Blaustein,2007+/Ca2+exchange inhibitors: A new class of calcium regulators.]]>7188198Kraft, R.,2007+/Ca 2+ exchange inhibitor KB-R7943 potently blocks TRPC channels.]]>361230236Liang, G.H., J.A. Kim, G.H. Seol, S. Choi and S.H. Suh,2008+/Ca2+ exchanger inhibitor KB-R7943 activates large-conductance Ca2+-activated K + channels in endothelial and vascular smooth muscle cells.]]>5823541Liang, G.H., M.Y. Kim, S. Park, J.A. Kim, S. Choi and S.H. Suh,2008+ modulates large conductance Ca2+-activated K+ currents in human umbilical vein endothelial cells.]]>4576775Liu, G., N. Dilmac, N. Hilliard and G.H. Hockerman,2003305271278MacDonald, P.E., J.W. Joseph and P. Rorsman,200536022112225Mears, D.,20042+ channels.]]>2005766Mitchell, K.J., F.A. Lai and G.A. Rutter,20032+ release from insulin-containing vesicles in living pancreatic beta-cells (MIN6).]]>2781105711064Nguidjoe, E., S. Sokolow, S. Bigabwa, N. Pachera and E. D'Amico et al.,20116020762085Numazawa, S., M. Takase, T. Ahiko, M. Ishii, S.I. Shimizu and T. Yoshida,201235346354Ouardouz, M., G.W. Zamponi, W. Barr, L. Kiedrowski and P.K. Stys,2005+/Ca 2+ exchange and L-type Ca 2+ channels.]]>48566575Pezier, A., Y.V. Bobkov and B.W. Ache,2009+/Ca2+ exchanger inhibitor, KB-R7943, blocks a nonselective cation channel implicated in chemosensory transduction.]]>10111511159Pintado, A.J., C.J. Herrero, A.G. Garcia and C. Montiel,2000+/Ca2+ exchange inhibitor KB‐R7943 also blocks native and expressed neuronal nicotinic receptors.]]>13018931902Pourkhalili, N., S. Pournourmohammadi, F. Rahimi, S. Vosough-Ghanbari, M. Baeeri, S.N. Ostad and M. 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