Weinhaus A J, Poronnik P, Cook D I, Tuch B E
Department of Medicine, University of Sydney, Australia.
Diabetes. 1995 Jan;44(1):118-24. doi: 10.2337/diab.44.1.118.
Fetal pancreatic islets release insulin poorly in response to glucose; however, the cellular mechanism for this is controversial. By using fura 2 to measure changes in the cytoplasmic free Ca2+ concentration ([Ca2+]i) in beta-cells, we have examined islets from fetal, neonatal, and adult rats to determine the ability of glucose and other secretagogues to cause an increase in [Ca2+]i. The effects of glucose (20 mmol/l), glyceraldehyde (20 mmol/l), leucine (20 mmol/l), arginine (20 mmol/l), and the channel effectors glipizide (50 mumol/l), BAY K8644 (2 mumol/l), diazoxide (300 mumol/l), and verapamil (20 mumol/l) on changes in [Ca2+]i were studied. In both the fetal and the mature islet, glyceraldehyde, leucine, arginine, glipizide, and BAY K8644 caused an increase in [Ca2+]i. In mature islets, glucose also increased [Ca2+]i; however, in the fetal islet, glucose had no effect on [Ca2+]i. The stimulus-induced increases in [Ca2+]i in fetal and adult islets were both significantly inhibited by the addition of either diazoxide or verapamil. Similar results were obtained when insulin secretion was measured. Our data show that various secretagogues are able to stimulate fetal islets and cause an increase in [Ca2+]i. Glucose, however, fails to cause an increase in [Ca2+]i in the fetal islet. Hence, the immature insulin secretory response to glucose by the fetal islet is due to the inability of the fetal beta-cell to translate glucose stimulation into the increase in [Ca2+]i required for exocytosis of the insulin granule.
胎儿胰岛对葡萄糖反应时胰岛素释放不佳；然而，其细胞机制存在争议。通过使用fura 2测量β细胞中细胞质游离Ca2+浓度（[Ca2+]i）的变化，我们检测了来自胎儿、新生和成年大鼠的胰岛，以确定葡萄糖和其他促分泌剂引起[Ca2+]i升高的能力。研究了葡萄糖（20 mmol/l）、甘油醛（20 mmol/l）、亮氨酸（20 mmol/l）、精氨酸（20 mmol/l）以及通道效应剂格列吡嗪（50 μmol/l）、BAY K8644（2 μmol/l）、二氮嗪（300 μmol/l）和维拉帕米（20 μmol/l）对[Ca2+]i变化的影响。在胎儿和成熟胰岛中，甘油醛、亮氨酸、精氨酸、格列吡嗪和BAY K8644均引起[Ca2+]i升高。在成熟胰岛中，葡萄糖也能升高[Ca2+]i；然而，在胎儿胰岛中，葡萄糖对[Ca2+]i无影响。添加二氮嗪或维拉帕米均可显著抑制胎儿和成年胰岛中刺激诱导的[Ca2+]i升高。测量胰岛素分泌时也得到了类似结果。我们的数据表明，各种促分泌剂能够刺激胎儿胰岛并导致[Ca2+]i升高。然而，葡萄糖未能使胎儿胰岛中的[Ca2+]i升高。因此，胎儿胰岛对葡萄糖的未成熟胰岛素分泌反应是由于胎儿β细胞无法将葡萄糖刺激转化为胰岛素颗粒胞吐所需的[Ca2+]i升高。
