生命早期饥饿和成年饱食糖代谢稳态失衡的同位素示踪研究

课题组前期研究发现生命早期经历饥饿继而成年经历饱食营养过剩（二次打击假说）与中国糖尿病高发的现状有关。目前中国尚有2亿贫困人口和8百万营养不良儿童，随着经济发展会经历营养改善甚至过剩，其面临的糖尿病风险不容忽视。探究二次打击下糖代谢紊乱发生机制对控制糖尿病发生具有重要意义。然而迄今未见系统地研究二次打击下与糖代谢紊乱密切相关的葡萄糖肠道吸收率、 肝脏输出率、组织的摄取率、葡萄糖出现率和消失率的病理生理改变。.本项目拟建立正常饮食组、早期正常饮食+成年高脂组、早期饥饿+成年正常饮食组和早期饥饿+成年高脂组SD大鼠模型，主要采用稳定性同位素示踪技术，完整地阐述生命早期饥饿和/或成年饱食血糖稳态（肠道葡萄糖吸收率、肝糖输出和组织葡萄糖摄取异常）以及肌肉胰岛素通路分子表达（GLUT4等）的改变，探讨其糖代谢稳态失衡的可能机制，为经历二次打击的人群预防糖尿病的发病提供科学依据。

In our previous study, we found that the rapid increase in the prevalence of diabetes in middle-aged and elderly people in China was associated with the combination of exposure to starvation during early life and overnutrition in adulthood (two hit hypothesis). Now there are still 200 million people in poverty and 8 million children with malnutrition in China and with the continuing economic development, they will have more food or even overnutrition. Therefore, their risk for diabetes should not be ignored. It has significant meaning to prevent diabetes that exploring the mechanism of glucose metabolism dysregulation after Two Hits (malnutrition followed by overnutrition). So far to our knowledge, no study has systematically explored the pathophysiological changes of intestinal glucose absorption, hepatic glucose production, peripheral tissue glucose uptake and the appearance and disappearance of glucose in the blood under the condition of malnutrition followed by overnutrition, all of which are closely related with glucose metabolism homeostasis..This study aims to demonstrate the mechanism of dysregulation of glucose metabolism homeostasis after starvation in early life followed by hyperphagia in adulthood. The SD rats will be divided into normal diet group, normal diet in early life+high fat diet in adulthood group, starvation in early life+normal diet in adulthood group and starvation in early life+high fat diet in adulthood group. We will detect the intestinal glucose absorption, hepatic glucose production, peripheral tissue glucose uptake in each group using isotope tracer technique and measure the expression of muscle insulin signaling molecules including insulin receptor, insulin receptor substrate-1 and glucose transporter 4. This project could provide scientific proof for preventing diabetes in people experiencing starvation in early life followed by hyperphagia in adulthood.