Malaisse W J, Lebrun P, Herchuelz A, Sener A, Malaisse-Lagae F
Endocrinology. 1983 Nov;113(5):1870-7. doi: 10.1210/endo-113-5-1870.
The tumor-promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and the hypoglycemic sulfonylurea gliclazide both stimulate insulin release from rat pancreatic islets incubated at a low concentration of glucose (2.8 mM). The increment in secretion rate evoked by the combination of these two secretagogues was at least 7 times higher than the sum of increments evoked by each agent alone. TPA augmented insulin release evoked by gliclazide more efficiently than that induced by glucose. The enhancing action of TPA could not be attributed solely to changes in the capacity of gliclazide to inhibit 86Rb outflow, to provoke an exchange between influent 40Ca and effluent 45Ca, or to stimulate the net uptake of 45Ca by the islets. Nevertheless, the facilitation by TPA of gliclazide-induced insulin release suggests that a biophysical interference with the handling of cations at the plasma membrane level represents the primary site of action of hypoglycemic sulfonylureas in the pancreatic B cell.
促肿瘤佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）和降血糖磺酰脲类药物格列齐特均可刺激在低葡萄糖浓度（2.8 mM）下孵育的大鼠胰岛释放胰岛素。这两种促分泌剂联合使用所引起的分泌速率增加至少比单独使用每种药物所引起的增加之和高7倍。TPA增强格列齐特诱发的胰岛素释放比增强葡萄糖诱发的更有效。TPA的增强作用不能仅仅归因于格列齐特抑制86Rb外流、引发流入的40Ca与流出的45Ca交换或刺激胰岛对45Ca的净摄取能力的变化。然而，TPA对格列齐特诱导的胰岛素释放的促进作用表明，在质膜水平对阳离子处理的生物物理干扰是降血糖磺酰脲类药物在胰腺β细胞中的主要作用位点。
