De Marinis L, Mancini A, Fiumara C, Camaioni M, Zuppi P, Conte G, Folli G
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy.
Diabetes Res. 1991 Jun;17(2):93-7.
It is known that insulin release is calcium-dependent and that calcium-antagonists, blocking calcium transport across cell membranes, inhibit it, especially interfering with the second phase of insulin secretion. Gallopamil (GAL) is a new calcium-antagonist that, although structurally similar to verapamil, has more potency. It blocks slow calcium channels and fast sodium channels. Even if it has been demonstrated in vitro, there is no evidence that GAL is able to impair the glucose-induced insulin release in humans. We have submitted five normal subjects (24-36 yr old) to oral glucose tolerance test (OGTT, 75 g of glucose p.o.) and OGTT plus GAL infusion test (1 mg i.v. as a bolus, followed by a 2 mg/hr infusion for 2.5 hr, starting 30 min before glucose load), in two different days, to determine the effects of GAL on insulin and C peptide release after oral glucose load. In opposite with verapamil effects, we found that GAL did not reduce the peak levels of insulin and C peptide, but the peak response was delayed and the incremental areas tended to increase during GAL infusion, so that an impairment of glucose tolerance was equally obtained. This study indicates that different calcium-antagonist drugs exert differential effects on insulin release and their action on glucose homeostasis should be kept in mind because of the large use of these drugs in cardiac patients.
已知胰岛素释放依赖于钙，而钙拮抗剂可阻断钙跨细胞膜的转运，从而抑制胰岛素释放，尤其会干扰胰岛素分泌的第二阶段。加洛帕米（GAL）是一种新型钙拮抗剂，尽管其结构与维拉帕米相似，但效力更强。它可阻断慢钙通道和快钠通道。即便在体外实验中已得到证实，但尚无证据表明GAL会损害人体葡萄糖诱导的胰岛素释放。我们让5名正常受试者（年龄在24至36岁之间）在两个不同的日子分别接受口服葡萄糖耐量试验（OGTT，口服75克葡萄糖）以及OGTT加GAL输注试验（静脉推注1毫克，随后在葡萄糖负荷前30分钟开始以2毫克/小时的速度输注2.5小时），以确定GAL对口服葡萄糖负荷后胰岛素和C肽释放的影响。与维拉帕米的作用相反，我们发现GAL并未降低胰岛素和C肽的峰值水平，但峰值反应延迟，且在GAL输注期间增量面积趋于增加，从而同样导致葡萄糖耐量受损。这项研究表明，不同的钙拮抗剂药物对胰岛素释放有不同的作用，鉴于这些药物在心脏病患者中的广泛使用，应牢记它们对葡萄糖稳态的影响。
