Nagamatsu S, Nakamichi Y, Katahira H
Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Diabetologia. 1997 Dec;40(12):1396-402. doi: 10.1007/s001250050841.
Recent studies have revealed that soluble N-ethylmaleimide sensitive factor attachment receptor (SNARE)-related proteins, originally identified in neural tissues, are also expressed in pancreatic beta cells. In this study, we investigated the effect of glucose on syntaxin 1 and alpha/beta SNAP biosynthesis in pancreatic beta cells and we demonstrated that syntaxin 1, but not alpha/beta SNAP biosynthesis by rat isolated pancreatic islets was stimulated specifically by glucose nearly in parallel with proinsulin biosynthesis. Stimulation of syntaxin 1 and proinsulin biosynthesis by glucose was dose-dependent (Km = approximately 8 mmol/l) and reached the maximum (about 8-12 fold) at concentrations over 11 mmol/l. In contrast, 22 mmol/l glucose increased alpha/beta SNAP biosynthesis about 2-fold only, similar to the increase in total protein synthesis. Stimulation of syntaxin 1 biosynthesis by glucose was also time-dependent, taking around 3 h to reach the maximum, and was not affected by actinomycin-D, suggesting regulation at the translational level. On the other hand, glucose had a similar stimulating effect on both syntaxin 1 and alpha/beta SNAP biosynthesis by mouse insulinoma betaTC3 cells as it did on proinsulin biosynthesis. The evidence showing coordinated stimulation of syntaxin 1 and proinsulin biosynthesis by glucose in rat islets suggested the critical functional role of syntaxin 1 in the insulin exocytotic mechanism.
最近的研究表明，最初在神经组织中发现的可溶性N - 乙基马来酰亚胺敏感因子附着受体（SNARE）相关蛋白，在胰腺β细胞中也有表达。在本研究中，我们研究了葡萄糖对胰腺β细胞中 syntaxin 1和α/β SNAP生物合成的影响，结果表明，大鼠分离的胰岛中，syntaxin 1的生物合成受到葡萄糖的特异性刺激，几乎与胰岛素原生物合成同步，而α/β SNAP的生物合成则未受影响。葡萄糖对syntaxin 1和胰岛素原生物合成的刺激呈剂量依赖性（Km约为8 mmol/l），在浓度超过11 mmol/l时达到最大值（约8 - 12倍）。相比之下，22 mmol/l葡萄糖仅使α/β SNAP生物合成增加约2倍，与总蛋白合成的增加相似。葡萄糖对syntaxin 1生物合成的刺激也是时间依赖性的，约3小时达到最大值，且不受放线菌素D的影响，提示在翻译水平上的调控。另一方面，葡萄糖对小鼠胰岛素瘤βTC3细胞中syntaxin 1和α/β SNAP生物合成的刺激作用与对胰岛素原生物合成的刺激作用相似。大鼠胰岛中葡萄糖对syntaxin 1和胰岛素原生物合成的协同刺激证据表明，syntaxin 1在胰岛素胞吐机制中具有关键的功能作用。
