Demerdash T M, Seyrek N, Smogorzewski M, Marcinkowski W, Nasser-Moadelli S, Massry S G
Division of Nephrology, University of Southern California, School of Medicine, Los Angeles, USA.
Kidney Int. 1996 Dec;50(6):2032-40. doi: 10.1038/ki.1996.526.
Basal levels of [Ca2+]i are elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for hyperglycemia-induced acute rise in polymorphonuclear leukocytes (PMNL), and explored whether such a rise is due to increased calcium entry into PMNL and/or to calcium release from their intracellular stores. There were dose dependent and time dependent rises in the [Ca2+]i of PMNL exposed to high concentrations of glucose. Similar effects were observed when the PMNL were exposed to high concentrations of choline chloride or mannitol. A substantial part of the rise in [Ca2+]i was inhibited when the media contained verapamil or nifedipine or when the PMNL were placed in calcium free media, and the rise in [Ca2+]i was completely abolished when the PMNL were placed in calcium free media containing ryanodine. GDP beta S or pertussis toxin almost completely prevented the glucose-induced rise in [Ca2+]i of PMNL. Rp-cAMP, H-89 or staurosporine produced significant inhibition of the rise in [Ca2+]i. High concentrations of glucose produced a dose dependent shrinkage of PMNL volume over a period of two hours. The volume of PMNL, however, was normal after 24 hours in vitro incubation studies as well as after 1, 2 and 12 days of streptozotocin-induced hyperglycemia in rats. The results are consistent with the formulation that the osmotic activity (cell shrinkage) of the high glucose concentrations activates G protein(s) which then stimulates the adenylate-cAMP-protein kinase A pathway, phospholipase C system and calcium channels. The stimulation of these cellular pathways permits both calcium influx into the PMNL as well as mobilization of calcium from their intracellular stores. Both of these events contribute to the acute rise in their [Ca2+]i. It is possible that the rise in [Ca2+]i is critical for the stimulation of the events that lead to the generation and accumulation of inorganic osmolytes to restore cell volume to normal.
糖尿病患者细胞内钙离子（[Ca2+]i）的基础水平升高。这种异常很可能是由于钙离子流入细胞增加以及该离子流出细胞减少所致。本研究检测了导致多形核白细胞（PMNL）因高血糖而急性升高的细胞途径，并探讨这种升高是否是由于进入PMNL的钙增加和/或其细胞内储存的钙释放所致。暴露于高浓度葡萄糖的PMNL的[Ca2+]i呈剂量依赖性和时间依赖性升高。当PMNL暴露于高浓度的氯化胆碱或甘露醇时，也观察到类似的效应。当培养基中含有维拉帕米或硝苯地平，或者将PMNL置于无钙培养基中时，[Ca2+]i的升高有很大一部分受到抑制；当将PMNL置于含有ryanodine的无钙培养基中时，[Ca2+]i的升高完全被消除。GDP-β-S或百日咳毒素几乎完全阻止了葡萄糖诱导的PMNL的[Ca2+]i升高。Rp-cAMP、H-89或星形孢菌素对[Ca2+]i的升高产生了显著抑制。高浓度葡萄糖在两小时内使PMNL体积呈剂量依赖性缩小。然而，在体外培养24小时后以及在链脲佐菌素诱导的大鼠高血糖1、2和12天后，PMNL的体积是正常的。结果与以下表述一致：高葡萄糖浓度的渗透活性（细胞收缩）激活G蛋白，然后刺激腺苷酸环化酶-cAMP-蛋白激酶A途径、磷脂酶C系统和钙通道。对这些细胞途径的刺激既允许钙离子流入PMNL，也允许从其细胞内储存中动员钙。这两个事件都导致了它们的[Ca2+]i急性升高。[Ca2+]i的升高可能对刺激导致无机渗透溶质产生和积累以将细胞体积恢复正常的事件至关重要。
