METABOLIC COROLLARIES IN ISLET TISSUE DURING TRANSPLANTATION

为了有助于增加理解和提高效率， 胰岛移植治疗I型和II型糖尿病 糖尿病是一种双管齐下的长期研究方法， 本方案项目的组成部分赠款： 1)定量组织化学（QH）将用于研究葡萄糖和 胰岛组织原位移植后的能量代谢 单糖和糖尿病动物。待研究的代谢参数 将包括葡萄糖转运、葡萄糖磷酸化、葡萄糖-6-磷酸化、葡萄糖转运蛋白和葡萄糖转运蛋白。 水解、细胞氧化还原和磷酸盐电位。的剂量和 胰岛的代谢状态和接受者的燃料体内平衡 将被操纵以发现决定移植的因素 生存I型（BB/W大鼠）和II型（BHEcdb大鼠）动物模型 糖尿病将被用于增强这种方法的相关性。的 研究将收集通过方法无法获得的重要新信息 通常用于研究移植过程中的胰岛。 2)使用腺病毒载体的现代基因工程技术将 完善以实现生物学和治疗上有用的 胰岛中葡萄糖代谢的改变， 移植一个重要的目标是降低免疫原性， 病毒载体基因工程将包括改变β细胞 葡萄糖激酶、葡萄糖-6-磷酸酶、乳酸脱氢酶和 甘油-β-脱氢酶，关键参与葡萄糖传感的酶。 胰岛组织基因操作的影响将首先 在体外评估，并且在β细胞转染的功效之后， 通过原位移植胰岛的OH分析， 以及评估移植的疗效。

In order to contribute to an increased understanding and highly efficacy of pancreatic islet transplantation as treatment of type I and type II diabetes a two pronged long range approach of research is outlined in the present component grant of the program project: 1) Quantitative Histochemistry (QH) will be applied to study glucose and energy metabolism of islet tissue in situ following transplantation into monoglycemic and diabetic animals. Parameters of metabolism to be studied will include glucose transport, glucose phosphorylation, glucose-6-P hydrolysis, the cellular redox and phosphate potentials. The dosage and metabolic state of the islet and the fuel homeostasis of the recipient will be manipulated to discover the factors that determine graft survival. Animal models of type I (BB/W rats) and type II (BHEcdb rats) diabetes will be used enhance the relevance in this approach. The research will gather important new information not obtainable by methods commonly applied to study islets during transplantation. 2) Modern techniques of genetic engineering using adenoviral vectors will be perfected to accomplish biologically and therapeutically useful alterations of glucose metabolism in islets that are to be used for transplantation. One important goal is reducing the immunogenicity of the viral vectors. Genetic engineering will include alterations of beta-cell glucokinase, glucose-6-phosphatase, lactic acid dehydrogenase and glycero-P-dehydrogenase, enzymes critically involved in glucose sensing. The impact of the genetic manipulation of islet tissue will be first assessed in vitro and the, after efficacy of the beta-cell transfection has been demonstrated, by OH analysis of the transplanted islet in situ and by evaluating the curative impact of the transplant.