Malaisse W J, Sener A, Herchuelz A, Carpinelli A R, Poloczek P, Winand J, Castagna M
Cancer Res. 1980 Oct;40(10):3827-31.
In isolated rat pancreatic islets, the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), when used in the 2.10(-9) to 2.10(-7) M range, was found to stimulate insulin release both in the absence and presence of glucose. The non-tumor-promoting agent 4-methylphorbol-12,13-didecanoate failed to stimulate insulin release. The insulinotropic capacity of TPA was enhanced by glucose in a dose-related fashion. In the absence of glucose, the TPA-stimulated release of insulin was a slowly induced and not rapidly reversible phenomenon. It was inhibited by antimycin A, by epinephrine, at low temperatures, and in the absence of extracellular Ca2+ or the presence of cytochalasin B, was unaffected by the organic calcium antagonist D600 or indomethacin, and was potentiated by theophylline. No obvious effect of TPA upon 86Rb or 32P efflux and 45Ca net uptake could be detected in the isolated islets. However, TPA caused a progressive increase in both 45Ca fractional outflow rate and cyclic adenosine 3':5'-monophosphate content in the islets. It is proposed that the insulinotropic action of TPA may be due, in part at least, to interference with the transport of calcium by native ionophores.
在分离的大鼠胰岛中，发现促肿瘤剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）在2×10⁻⁹至2×10⁻⁷M范围内使用时，无论有无葡萄糖存在均能刺激胰岛素释放。非促肿瘤剂4 - 甲基佛波醇 - 12,13 - 二癸酸酯不能刺激胰岛素释放。TPA的促胰岛素释放能力在有葡萄糖存在时呈剂量相关方式增强。在无葡萄糖时，TPA刺激的胰岛素释放是一种缓慢诱导且不可逆的现象。它受到抗霉素A、肾上腺素的抑制，在低温下，以及在无细胞外Ca²⁺或有细胞松弛素B存在时受到抑制，不受有机钙拮抗剂D600或吲哚美辛的影响，且被茶碱增强。在分离的胰岛中未检测到TPA对⁸⁶Rb或³²P外流以及⁴⁵Ca净摄取有明显影响。然而，TPA导致胰岛中⁴⁵Ca分数流出率和环磷酸腺苷含量逐渐增加。有人提出，TPA的促胰岛素释放作用可能至少部分归因于对天然离子载体介导的钙转运的干扰。
