Fadda G Z, Thanakitcharu P, Massry S G
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Proc Soc Exp Biol Med. 1991 Nov;198(2):742-6. doi: 10.3181/00379727-198-43313.
Potassium-induced insulin secretion is impaired in rats with chronic renal failure and a sustained rise in cytosolic calcium ([Ca2+]i). It has been found that the calcium signal (delta[Ca2+]i) and the delta [Ca2+]i/basal [Ca2+]i in these animals in response to potassium are smaller than those in normal rats and that these defects may underlie, at least in part, the reduced potassium-induced insulin secretion, since the latter depends on an appropriate rise in [Ca2+]i. Since phosphate depletion (PD) is another model associated with a rise in the basal level of [Ca2+]i of pancreatic islets, it provides another metabolic setting for investigating the interaction between high [Ca2+]i of islets and their response to potassium. We examined the potassium-induced insulin secretion, the potassium-induced calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in islets of PD rats with and without elevated [Ca2+]i. The levels of the basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) higher than those in pair-weighed (PW) animals and those in PD and PW rats treated with verapamil, which has been shown to prevent the rise in [Ca2+]i in islets of PD rats. Both initial and total insulin secretion, the calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) smaller than those in the other three groups of animals. There were no significant differences in basal levels of [Ca2+]i and in calcium signal, delta [Ca2+]i/basal [Ca2+]i, and insulin secretion among PW rats, verapamil-treated PD rats, and verapamil-treated PW rats. The results are consistent with the notion that elevated resting levels of [Ca2+]i interfere with the magnitude of the calcium signal and the ratio of calcium signal to basal [Ca2+]i, and these derangements, at least in part, underlie the impaired potassium-induced insulin secretion in PD.
慢性肾衰竭大鼠存在钾诱导的胰岛素分泌受损以及胞质钙（[Ca2+]i）持续升高的情况。已发现这些动物对钾反应时的钙信号（δ[Ca2+]i）以及δ[Ca2+]i/基础[Ca2+]i比正常大鼠小，并且这些缺陷可能至少部分是钾诱导的胰岛素分泌减少的原因，因为后者依赖于[Ca2+]i的适当升高。由于磷酸盐耗竭（PD）是另一种与胰岛[Ca2+]i基础水平升高相关的模型，它为研究胰岛高[Ca2+]i与其对钾反应之间的相互作用提供了另一种代谢环境。我们检查了有或无[Ca2+]i升高的PD大鼠胰岛中钾诱导的胰岛素分泌、钾诱导的钙信号以及δ[Ca2+]i/基础[Ca2+]i。PD大鼠胰岛中的基础[Ca2+]i水平显著高于配对体重（PW）动物以及用维拉帕米治疗的PD和PW大鼠（P＜0.01），维拉帕米已被证明可防止PD大鼠胰岛中[Ca2+]i升高。PD大鼠胰岛中的初始和总胰岛素分泌、钙信号以及δ[Ca2+]i/基础[Ca2+]i均显著低于其他三组动物（P＜0.01）。PW大鼠、维拉帕米治疗的PD大鼠和维拉帕米治疗的PW大鼠之间的基础[Ca2+]i水平、钙信号、δ[Ca2+]i/基础[Ca2+]i以及胰岛素分泌均无显著差异。这些结果与以下观点一致，即升高的[Ca2+]i静息水平会干扰钙信号的幅度以及钙信号与基础[Ca2+]i的比值，并且这些紊乱至少部分是PD中钾诱导的胰岛素分泌受损的原因。
