Hajjar S M, Fadda G Z, Thanakitcharu P, Smogorzewski M, Massry S G
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
J Am Soc Nephrol. 1992 Feb;2(8):1355-9. doi: 10.1681/ASN.V281355.
The activity of Na(+)-K+ ATPase of pancreatic islets modulates their insulin secretion. The study presented here examined the activity of this enzyme in pancreatic islets of chronic renal failure (CRF) rats in an effort to further delineate the mechanisms of impaired insulin secretion in CRF. The Vmax of Na(+)-K+ ATPase, but not its Km, and the ATP content are significantly reduced in islets of CRF rats that have elevated levels of parathyroid hormone (PTH). These derangements are prevented by prior parathyroidectomy of CRF rats (low blood levels of PTH) or by their treatment with the calcium channel blocker verapamil; these latter rats have sustained elevation of blood levels of PTH. The data indicate that the chronic excess blood levels of PTH in CRF initiates events (augmented entry of calcium) that lead to the reduction in ATP content and in Vmax of Na(+)-K+ ATPase of pancreatic islets. Reducing the blood levels of PTH by parathyroidectomy or blocking the action of PTH on calcium entry into cells by verapamil prevents these derangements. The results suggest that chronic inhibition of Na(+)-K+ ATPase may participate in the processes underlying the impaired insulin secretion in CRF.
胰岛的钠钾ATP酶活性可调节胰岛素分泌。本文的研究检测了慢性肾衰竭（CRF）大鼠胰岛中该酶的活性，以进一步阐明CRF中胰岛素分泌受损的机制。在甲状旁腺激素（PTH）水平升高的CRF大鼠胰岛中，钠钾ATP酶的最大反应速度（Vmax）显著降低，而其米氏常数（Km）及ATP含量未受影响。预先切除CRF大鼠的甲状旁腺（PTH血水平降低）或用钙通道阻滞剂维拉帕米治疗（PTH血水平持续升高）可防止这些紊乱。数据表明，CRF中慢性升高的PTH血水平引发了一系列事件（钙内流增加），导致胰岛ATP含量及钠钾ATP酶Vmax降低。通过甲状旁腺切除降低PTH血水平或用维拉帕米阻断PTH对细胞钙内流的作用可防止这些紊乱。结果提示，慢性抑制钠钾ATP酶可能参与了CRF中胰岛素分泌受损的潜在机制。
