Iida-Klein A, Hahn T J
Geriatric Research, Education, and Clinical Center, Wadsworth VA Medical Center, Los Angeles, California.
Endocrinology. 1991 Aug;129(2):1016-24. doi: 10.1210/endo-129-2-1016.
Insulin modifies the effects of PTH on osteoblast-like cells. However, the basis for this effect is unknown. In bone and kidney cells, the effects of PTH on cellular function are mediated by second messengers generated through both the phospholipase C and adenylate cyclase systems. Therefore, we examined the effects of insulin on PTH second messenger generation in UMR-106-01 rat osteoblastic osteosarcoma cells. PTH produced a rapid, transient increase in intracellular free calcium concentration ([Ca2+]i) which was maximal at 30 sec and was only minimally reduced in the absence of extracellular calcium. Inositol-triphosphate (IP3) production was increased in parallel. PTH stimulation of [Ca2+]i was concentration-dependent from 0.5-1,000 nM, with half-maximal stimulation at approximately 50 nM PTH. A 30-sec exposure to 50 nM PTH produced 32% and 23% increases in IP1 and IP3 production, respectively (both P less than 0.05). Although insulin alone did not significantly alter basal [Ca2+]i, a 1-min exposure to 1-100 nM insulin produced a concentration-dependent suppression of the PTH-stimulated transient increase in [Ca2+]i and IP3 generation. 100 nM insulin decreased 50 nM PTH stimulation of [Ca2+]i and IP3 levels by 84% (P less than 0.02) and 80% (P less than 0.001), respectively. Preexposure to insulin also decreased PTH stimulation of intracellular cAMP levels, but to a lesser degree. A 1-min exposure to 100 nM insulin produced a 32% (P less than 0.01) decrease in PTH-stimulated cAMP generation, but lower insulin concentrations were without significant effects. These results demonstrate that in UMR-106-01 cells, insulin suppresses PTH stimulation of second messengers generated through both the phospholipase C and adenylate cyclase systems, but has a more marked effect on the former.
胰岛素可改变甲状旁腺激素（PTH）对成骨样细胞的作用。然而，这种作用的基础尚不清楚。在骨细胞和肾细胞中，PTH对细胞功能的作用是由通过磷脂酶C和腺苷酸环化酶系统产生的第二信使介导的。因此，我们研究了胰岛素对UMR-106-01大鼠成骨细胞骨肉瘤细胞中PTH第二信使生成的影响。PTH使细胞内游离钙浓度（[Ca2+]i）迅速短暂升高，在30秒时达到最大值，在无细胞外钙的情况下仅略有降低。肌醇三磷酸（IP3）的生成也平行增加。PTH对[Ca2+]i的刺激在0.5 - 1000 nM范围内呈浓度依赖性，在约50 nM PTH时达到半最大刺激。暴露于50 nM PTH 30秒分别使IP1和IP3生成增加32%和23%（均P < 0.05）。虽然单独的胰岛素不会显著改变基础[Ca2+]i，但暴露于1 - 100 nM胰岛素1分钟会产生浓度依赖性抑制PTH刺激的[Ca2+]i和IP3生成的短暂升高。100 nM胰岛素使50 nM PTH对[Ca2+]i和IP3水平的刺激分别降低84%（P < 0.02）和80%（P < 0.001）。预先暴露于胰岛素也会降低PTH对细胞内cAMP水平的刺激，但程度较小。暴露于100 nM胰岛素1分钟会使PTH刺激的cAMP生成降低32%（P < 0.01），但较低浓度的胰岛素没有显著影响。这些结果表明，在UMR-106-01细胞中，胰岛素抑制PTH对通过磷脂酶C和腺苷酸环化酶系统产生的第二信使的刺激，但对前者的影响更明显。
