Verspohl E J, Wunderle G, Ammon H P, Williams J A, Goldfine I D
Naunyn Schmiedebergs Arch Pharmacol. 1986 Mar;332(3):284-7. doi: 10.1007/BF00504868.
CCK-8 and its desulfated analog (des-CCK-8) increase insulin secretion from isolated rat pancreatic islets in the presence of 8.3 mM glucose in a concentration-dependent manner. Proglumide (DL-4-benzamido-N,N-dipropylglutaramic acid), a gastrin and cholecystokinin (CCK) receptor antagonist, inhibits the synergistic effect of CCK on insulin release in the presence of 8.3 mM glucose; its EC50 (half-maximal effective concentration) was 1.2 +/- 0.4 mM. Its effect is specific in that it does not inhibit the glucose- or GIP (glucose dependent insulinotropic peptide) induced insulin secretion to a major degree. CCK-8, des-CCK-8 and proglumide compete for binding of 125I-CCK-33 to rat pancreatic islets; the IC50 of proglumide was 0.8 mM. The affinity of proglumide is in the range of both its EC50 for inhibition of insulin secretion and its IC50 in other in vitro systems tested so far (exocrine pancreas, gall bladder, cortex). Its inhibitory effect presumably is not a gastrin antagonizing effect since gastrin does not stimulate insulin secretion. The data therefore indicate that proglumide should be monitored for diabetic effects in vivo.
在存在8.3 mM葡萄糖的情况下，CCK - 8及其去硫酸化类似物（去CCK - 8）以浓度依赖的方式增加分离的大鼠胰岛的胰岛素分泌。丙谷胺（DL - 4 - 苯甲酰胺基 - N，N - 二丙基戊二酸），一种胃泌素和胆囊收缩素（CCK）受体拮抗剂，在存在8.3 mM葡萄糖的情况下抑制CCK对胰岛素释放的协同作用；其EC50（半数最大有效浓度）为1.2±0.4 mM。其作用具有特异性，因为它在很大程度上不抑制葡萄糖或GIP（葡萄糖依赖性促胰岛素多肽）诱导的胰岛素分泌。CCK - 8、去CCK - 8和丙谷胺竞争125I - CCK - 33与大鼠胰岛的结合；丙谷胺的IC50为0.8 mM。丙谷胺的亲和力在其抑制胰岛素分泌的EC50和迄今为止在其他体外系统（外分泌胰腺、胆囊、皮质）中测试的IC50范围内。其抑制作用可能不是胃泌素拮抗作用，因为胃泌素不刺激胰岛素分泌。因此，数据表明应该在体内监测丙谷胺对糖尿病的影响。
