Fadda G Z, Massry S G
Division of Nephrology, University of Southern California School of Medicine, Los Angeles.
Am J Nephrol. 1991;11(6):475-8. doi: 10.1159/000168362.
Basal level of cytosolic calcium ([Ca2+]i) is elevated in islets of rats with chronic renal failure (CRF). The high [Ca2+]i level was implicated in the impaired insulin secretion of CRF, and its effect is due, in part, to a reduction in ATP content and impaired glucose metabolism by the islets. However, elevated [Ca2+]i may interfere with insulin secretion via another pathway. Exposure of the islets to glucose causes an acute rise in [Ca2+]i which generates events leading to insulin secretion. It is possible that a sustained rise in [Ca2+]i interferes with the magnitude of glucose-induced calcium signal and the ratio between this signal and basal [Ca2+]i. We examined this question in normal, CRF, normocalcemic CRF-PTX rats and in CRF rats treated with verapamil (CRF-V). Basal [Ca2+]i was higher (p less than 0.01) in CRF (130 +/- 7.0 nM) than in normal (82 +/- 5.5 nM), CRF-PTX (75 +/- 3.6 nM) and CRF-V rats (84 +/- 3.8 nM). Glucose-induced calcium signal (95 +/- 10.4 nM) and the ratio between this signal and basal [Ca2+]i (0.73 +/- 0.07) in CRF rats were lower (p less than 0.01) than in normal (153 +/- 14.4 nM; 1.90 +/- 0.24), CRF-PTX (130 +/- 16.7 nM; 1.75 +/- 0.25) and CRF-V (124 +/- 5.8 nM; 1.90 +/- 0.12) rats despite high PTH in the latter. The data indicate that a sustained rise in [Ca2+]i of islets interferes with the glucose-induced calcium signal which in turn plays a role in impaired insulin secretion.
慢性肾功能衰竭（CRF）大鼠胰岛中细胞溶质钙（[Ca2+]i）的基础水平升高。较高的[Ca2+]i水平与CRF时胰岛素分泌受损有关，其作用部分归因于胰岛中ATP含量降低和葡萄糖代谢受损。然而，升高的[Ca2+]i可能通过另一条途径干扰胰岛素分泌。将胰岛暴露于葡萄糖会导致[Ca2+]i急性升高，进而引发导致胰岛素分泌的一系列事件。持续升高的[Ca2+]i有可能干扰葡萄糖诱导的钙信号强度以及该信号与基础[Ca2+]i之间的比率。我们在正常大鼠、CRF大鼠、血钙正常的CRF - PTX大鼠以及用维拉帕米治疗的CRF大鼠（CRF - V）中研究了这个问题。CRF大鼠（130±7.0 nM）的基础[Ca2+]i高于正常大鼠（82±5.5 nM）、CRF - PTX大鼠（75±3.6 nM）和CRF - V大鼠（84±3.8 nM）（p<0.01）。CRF大鼠中葡萄糖诱导的钙信号（95±10.4 nM）以及该信号与基础[Ca2+]i的比率（0.73±0.07）低于正常大鼠（153±14.4 nM；1.90±0.24）、CRF - PTX大鼠（130±16.7 nM；1.75±0.25）和CRF - V大鼠（124±5.8 nM；1.90±0.12）（p<0.01），尽管后三者甲状旁腺激素水平较高。数据表明，胰岛中[Ca2+]i的持续升高会干扰葡萄糖诱导的钙信号，而这反过来又在胰岛素分泌受损中起作用。
