Kato I, Suzuki Y, Akabane A, Yonekura H, Tanaka O, Kondo H, Takasawa S, Yoshimoto T, Okamoto H
Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Ann N Y Acad Sci. 1996 Dec 26;805:232-42; discussion 242-3. doi: 10.1111/j.1749-6632.1996.tb17486.x.
Using transgenic mice technology, it has now become possible to test directly whether VIP and PHM-27 can enhance glucose-induced insulin secretion and reduce blood glucose in vivo. By microinjecting the entire human VIP gene ligated to the rat insulin II promoter, we have established a mouse model that overproduces VIP and PHM-27 in pancreatic beta cells. VIP was secreted from transgenic islets in a glucose-dependent manner. Analyses of these VIP-transgenic mice indicated that the transgene efficiently enhances glucose-induced insulin secretion and significantly reduces blood glucose as compared with control mice. The transgene also ameliorated glucose intolerance of 70% depancreatized mice. The present results suggest that somatic cell gene therapy directed to diabetic islets by human VIP/PHM-27 gene introduction may provide a means to improve the secretory function of the diabetic islets.
利用转基因小鼠技术，现在已经能够直接测试血管活性肠肽（VIP）和PHM - 27是否可以在体内增强葡萄糖诱导的胰岛素分泌并降低血糖。通过显微注射连接到大鼠胰岛素II启动子的整个人类VIP基因，我们建立了一种在胰腺β细胞中过量产生VIP和PHM - 27的小鼠模型。VIP以葡萄糖依赖的方式从转基因胰岛中分泌出来。对这些VIP转基因小鼠的分析表明，与对照小鼠相比，转基因有效地增强了葡萄糖诱导的胰岛素分泌并显著降低了血糖。该转基因还改善了70%胰腺切除小鼠的葡萄糖不耐受性。目前的结果表明，通过引入人类VIP/PHM - 27基因针对糖尿病胰岛进行体细胞基因治疗可能提供一种改善糖尿病胰岛分泌功能的方法。
