Wiedenkeller D E, Sharp G W
Endocrinology. 1984 Jan;114(1):116-9. doi: 10.1210/endo-114-1-116.
Insulin release from rat pancreatic islets, stimulated by cAMP, 3-isobutyl-1-methylxanthine, or forskolin, is potentiated by TMB-8 [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate], a drug that blocks the efflux of calcium from intracellular calcium stores without affecting influx. There is a short latent period before the potentiation occurs which can be reduced by preincubation with the drug. TMB-8 alone neither stimulates nor inhibits insulin release. The results suggest that an intracellular store fills with calcium because of the blocked efflux and unchanged influx, and loses its ability to regulate the cytosol Ca++ concentration. Under basal conditions, in the presence or absence of TMB-8, the plasma membrane is able to regulate the cytosol Ca++ concentration at low levels so that no change in insulin release occurs. However, when 3-isobutyl-1-methylxanthine, cAMP, or forskolin add an additional Ca++ load to the cytosol, the regulator capacity of the plasma membrane is overwhelmed, and cytosol Ca++ rises to higher levels than in the absence of TMB-8 because the filled store is no longer regulating. Thus, insulin release is potentiated.
由环磷酸腺苷（cAMP）、3-异丁基-1-甲基黄嘌呤或福斯可林刺激的大鼠胰岛胰岛素释放，可被TMB-8 [8-(N,N-二乙氨基)辛基3,4,5-三甲氧基苯甲酸酯]增强，TMB-8是一种能阻断细胞内钙库钙外流而不影响钙内流的药物。在增强作用发生前有一个短暂的潜伏期，预先用该药物孵育可缩短此潜伏期。单独使用TMB-8既不刺激也不抑制胰岛素释放。结果表明，由于外流受阻而内流不变，细胞内钙库充满了钙，并失去了调节胞质溶胶Ca++浓度的能力。在基础条件下，无论有无TMB-8，质膜都能够在低水平调节胞质溶胶Ca++浓度，从而胰岛素释放无变化。然而，当3-异丁基-1-甲基黄嘌呤、cAMP或福斯可林向胞质溶胶中额外添加Ca++负荷时，质膜的调节能力不堪重负，且由于充满钙的钙库不再发挥调节作用，胞质溶胶Ca++上升到比无TMB-8时更高的水平。因此，胰岛素释放增强。
