Hennige Anita M, Fritsche Andreas, Strack Volker, Weigert Cora, Mischak Harald, Borboni Patricia, Renn Walter, Häring Hans-Ulrich, Kellerer Monika
Department of Internal Medicine IV, University of Tübingen, Otfried-Mueller-Strasse 10, D-72076 Tübingen, Germany.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):85-90. doi: 10.1006/bbrc.2001.6144.
Protein kinase C seems to be linked to the regulation of insulin secretion as well as mitogenic signaling in pancreatic beta cells. To study the impact of different PKC isoforms on insulin secretion and mitogenic activity we stably overexpressed the PKC isoforms alpha, beta2, epsilon, and zeta in the rat clonal beta cell line RIN 1046-38. Under basal conditions PKC alpha, beta2, epsilon, and zeta were identified mainly in the cytosol. Treatment with the phorbol ester TPA caused translocation of PKC alpha, beta2, and epsilon to the plasma membrane. Glucose- and TPA-dependent increases in insulin release were comparable in all cell lines regardless of whether PKC was overexpressed or not. While PKC isoforms alpha, beta2, and epsilon had no effect on the [(3)H]thymidine incorporation rate, overexpression of PKC zeta specifically increased basal as well as IGF-1-dependent [(3)H]thymidine incorporation. Incubation with the MAP-kinase inhibitor PD98056 abolished this effect. Furthermore, treatment with IGF-1 led to activation of the beta cell-specific transcription factor PDX-1 in RIN 1046-38 cells overexpressing PKC zeta. Our data suggest that PKC zeta is involved in basal as well as IGF-1-dependent mitogenesis in RIN 1046-38 cells, while none of the PKC isoforms tested seem to be related to glucose-stimulated insulin release.
蛋白激酶C似乎与胰腺β细胞中胰岛素分泌的调节以及促有丝分裂信号传导有关。为了研究不同蛋白激酶C亚型对胰岛素分泌和促有丝分裂活性的影响，我们在大鼠克隆β细胞系RIN 1046 - 38中稳定过表达了蛋白激酶C亚型α、β2、ε和ζ。在基础条件下，蛋白激酶Cα、β2、ε和ζ主要定位于细胞质中。用佛波酯TPA处理导致蛋白激酶Cα、β2和ε转位至质膜。无论蛋白激酶C是否过表达，所有细胞系中葡萄糖和TPA依赖性胰岛素释放的增加都是相当的。虽然蛋白激酶C亚型α、β2和ε对[³H]胸腺嘧啶掺入率没有影响，但蛋白激酶Cζ的过表达特异性增加了基础以及IGF - 1依赖性的[³H]胸腺嘧啶掺入。用MAP激酶抑制剂PD98056孵育可消除这种效应。此外，用IGF - 1处理导致在过表达蛋白激酶Cζ的RIN 1046 - 38细胞中β细胞特异性转录因子PDX - 1的激活。我们的数据表明，蛋白激酶Cζ参与RIN 1046 - 38细胞中的基础以及IGF - 1依赖性的有丝分裂发生，而所测试的任何蛋白激酶C亚型似乎都与葡萄糖刺激的胰岛素释放无关。
