Gronda C M, Diaz G B, Rossi J P, Gagliardino J J
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET), Facultad de Ciencias Médicas, La Plata, Argentina.
J Endocrinol. 1992 Aug;134(2):221-5. doi: 10.1677/joe.0.1340221.
Using medium with a low ionic strength, a low concentration of Ca2+ and Mg2+ and devoid of K+, we have measured Ca(2+)-ATPase activity in the homogenates of rat islets preincubated for 3 min with several hormones in the presence of 3.3 mmol glucose/l. Insulin secretion was also measured in islets incubated for 5 min under identical experimental conditions. Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly. Dexamethasone (0.1 mumol/l) and somatostatin (1.2 mumol/l) enhanced the Ca(2+)-ATPase activity while adrenaline (10 mumol/l) did not produce any significant effect on the activity of the enzyme. These hormones decreased the release of insulin significantly. These results demonstrated that islet Ca(2+)-ATPase activity was modulated by the hormones tested. Their inhibitory or enhancing effect seemed to be related to their effect on insulin secretion; i.e. those which stimulated the secretion of insulin inhibited the activity of the enzyme and vice versa. Hence, their effect on insulin secretion may be due, in part, to their effect on enzyme activity and consequently on the concentration of cytosolic Ca2+. These results reinforce the assumption that Ca(2+)-ATPase activity participates in the physiological regulation of insulin secretion, being one of the cellular targets for several agents which affect this process.
使用离子强度低、Ca2+和Mg2+浓度低且不含K+的介质,我们在3.3 mmol葡萄糖/升存在的情况下,对预先与几种激素孵育3分钟的大鼠胰岛匀浆中的Ca(2+)-ATP酶活性进行了测量。在相同实验条件下孵育5分钟的胰岛中也测量了胰岛素分泌。预先与葡萄糖(3.3 mmol/升)、胰高血糖素(1.4 μmol/升)加茶碱(10 mmol/升)、促肾上腺皮质激素(0.11 nmol/升)、牛生长激素(0.46 μmol/升)、催乳素(0.2 μmol/升)或三碘甲状腺原氨酸(1.0 nmol/升)孵育的胰岛,其Ca(2+)-ATP酶活性显著低于仅预先与3.3 mmol葡萄糖/升孵育的胰岛。所有这些激素均显著增加了胰岛素的释放。地塞米松(0.1 μmol/升)和生长抑素(1.2 μmol/升)增强了Ca(2+)-ATP酶活性,而肾上腺素(10 μmol/升)对该酶的活性没有产生任何显著影响。这些激素显著降低了胰岛素的释放。这些结果表明,胰岛Ca(2+)-ATP酶活性受到所测试激素的调节。它们的抑制或增强作用似乎与其对胰岛素分泌的影响有关;即那些刺激胰岛素分泌的激素抑制了该酶的活性,反之亦然。因此,它们对胰岛素分泌的影响可能部分归因于它们对酶活性的影响,进而对细胞质Ca2+浓度的影响。这些结果强化了这样一种假设,即Ca(2+)-ATP酶活性参与胰岛素分泌的生理调节,是影响这一过程的几种药物的细胞靶点之一。