Drews G, Debuyser A, Nenquin M, Henquin J C
I Physiologisches Institut, University of Saarland, Homburg/Saar, West Germany.
Endocrinology. 1990 Mar;126(3):1646-53. doi: 10.1210/endo-126-3-1646.
The mechanisms by which galanin and epinephrine affect pancreatic B-cell function were studied in normal mouse islets. In the presence of 15 mM glucose and 2.5 mM Ca2+, galanin (50 nM) and epinephrine (100 nM) hyperpolarized the B-cell membrane and suppressed electrical activity only transiently. These changes were accompanied by a decrease in 86Rb+ efflux from islet cells and nearly complete inhibition of insulin release. Both agents also decreased 86Rb+ efflux in the absence of Ca2+. Low concentrations (10-15 microM) of diazoxide, an activator of ATP-sensitive K+ channels, mimicked some effects of galanin and epinephrine. However, insulin release was more markedly inhibited by galanin or epinephrine than by diazoxide when electrical activity was similarly decreased, and diazoxide had no effect on 86Rb+ efflux in the absence of Ca2+. When the permeability to K+ was increased by 100 microM diazoxide and the hyperpolarization reversed by high extracellular K+, galanin and epinephrine still inhibited insulin release, but did not affect the membrane potential or 86Rb+ efflux. Galanin and epinephrine decreased glucose utilization and oxidation in islet cells by about 10%, whereas diazoxide had no effect. Blockade of alpha 2-adrenoceptors by yohimbine suppressed the effects of epinephrine, but not those of galanin. It is concluded that activation of galanin and alpha2-adrenergic receptors inhibits insulin release by the same mechanisms. These may involve an increase in K+ permeability of the B-cell membrane by opening ATP-sensitive K+ channels and an additional effect independent of the membrane potential.
在正常小鼠胰岛中研究了甘丙肽和肾上腺素影响胰腺β细胞功能的机制。在存在15 mM葡萄糖和2.5 mM Ca2+的情况下，甘丙肽（50 nM）和肾上腺素（100 nM）使β细胞膜超极化，并仅短暂抑制电活动。这些变化伴随着胰岛细胞86Rb+外流减少以及胰岛素释放几乎完全被抑制。两种药物在无Ca2+时也降低了86Rb+外流。低浓度（10 - 15 microM）的二氮嗪，一种ATP敏感性钾通道激活剂，模拟了甘丙肽和肾上腺素的一些作用。然而，当电活动类似降低时，甘丙肽或肾上腺素对胰岛素释放的抑制比二氮嗪更明显，并且二氮嗪在无Ca2+时对86Rb+外流无影响。当用100 microM二氮嗪增加钾通透性且用高细胞外钾逆转超极化时，甘丙肽和肾上腺素仍抑制胰岛素释放，但不影响膜电位或86Rb+外流。甘丙肽和肾上腺素使胰岛细胞中的葡萄糖利用和氧化减少约10%，而二氮嗪无此作用。育亨宾阻断α2 - 肾上腺素能受体可抑制肾上腺素的作用，但不影响甘丙肽的作用。结论是甘丙肽和α2 - 肾上腺素能受体的激活通过相同机制抑制胰岛素释放。这些机制可能包括通过打开ATP敏感性钾通道增加β细胞膜的钾通透性以及一种独立于膜电位的额外作用。
