Genetically engineered K cells provide sufficient insulin to correct hyperglycemia in a nude murine model  

作　　者：Yiqun Zhang Liqing Yao Kuntang Shen Meidong Xu Pinghong Zhou Weige Yang Xinyuan Liu Xinyu Qin 

机构地区：[1]Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China [2]Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

出　　处：《Acta Biochimica et Biophysica Sinica》2008年第2期149-157,共9页生物化学与生物物理学报（英文版）

摘　　要：A gene therapy-based treatment of type 1 diabetes mellitus requires the development of a surrogate β cell that can synthesize and secrete functionally active insulin in response to physiologically relevant changes in ambient glucose levels. In this study, the murine enteroendocrine cell line STC-1 was genetically modified by stable transfection. Two clone cells were selected （STC-1-2 and STC-1-14） that secreted the highest levels of insulin among the 22 clones expressing insulin from 0 to 157.2 μIU/ml/10^6 cells/d. After glucose concentration in the culture medium was increased from 1 mM to 10 mM, secreted insulin rose from 40.3±0.8 to 56.3±3.2 μIU/ml （STC-1-2）, and from 10.8±0.8 to 23.6±2.3 μIU/ml （STC- 1-14）. After STC-1-14 cells were implanted into diabetic nude mice, their blood glucose levels were reduced to normal. Body weight loss was also ameliorated. Our data suggested that genetically engineered K cells secrete active insulin in a glucose-regulated manner, and in vivo study showed that hyperglycemia could be reversed by implantation of the cells, suggesting that the use of genetically engineered K cells to express human insulin might provide a glucose-regulated approach to treat diabetic hyperglycemia.A gene therapy-based treatment of type 1 diabetes mellitus requires the development of a surrogate β cell that can synthesize and secrete functionally active insulin in response to physiologically relevant changes in ambient glucose levels. In this study, the murine enteroendocrine cell line STC-1 was genetically modified by stable transfection. Two clone cells were selected （STC-1-2 and STC-1-14） that secreted the highest levels of insulin among the 22 clones expressing insulin from 0 to 157.2 μIU/ml/10^6 cells/d. After glucose concentration in the culture medium was increased from 1 mM to 10 mM, secreted insulin rose from 40.3±0.8 to 56.3±3.2 μIU/ml （STC-1-2）, and from 10.8±0.8 to 23.6±2.3 μIU/ml （STC- 1-14）. After STC-1-14 cells were implanted into diabetic nude mice, their blood glucose levels were reduced to normal. Body weight loss was also ameliorated. Our data suggested that genetically engineered K cells secrete active insulin in a glucose-regulated manner, and in vivo study showed that hyperglycemia could be reversed by implantation of the cells, suggesting that the use of genetically engineered K cells to express human insulin might provide a glucose-regulated approach to treat diabetic hyperglycemia.

关 键 词：type 1 diabetes mellitus INSULIN GENETHERAPY glucose-dependent insulinotropic polypeptide STC-1 cell glucose 

分 类 号：R587.1[医药卫生—内分泌]