胃旁路术后小肠糖代谢重构对肝糖输出的调控研究

Gastric bypass surgery have been shown to induce rapid and long-term remission of diabetes, However, the underlying mechanisms are still undefined. Our previous studies have shown that gastric bypass surgery alters the anatomy and physiology of the small intestine resulting in the reconstruction of intestinal glucose metabolism (the enhancement of intestinal gluconeogenesis), which is associated with reduced hepatic glucose production. Other studies showed that the perception of nutrients change by sweet taste receptors in the small intestine has an important role in regulation of energy metabolism and glucose homeostasis. Based on the above studies, it is speculated that the reconstruction of intestinal glucose metabolism (the enhancement of intestinal gluconeogenesis) upload the signals through the perception of sweet taste receptors in the small intestine to regulate the hepatic glucose production. This study is conducted to confirm the regulation of hepatic glucose production by reconstruction of intestinal glucose metabolism and the perception of sweet taste receptors in the small intestine, using intestinal perfusion, extracellular microelectrode recording, extended hyperinsulinemic-euglycemic clamp experiments and other research techniques on Goto-kakizaki rats after duodenal-jejunal bypass surgery. This study aims to explore the regulation of hepatic glucose production by reconstruction of intestinal glucose metabolism and the perception of sweet taste receptors , further revealing the role of gut in the mechanisms of diabetes remission after gastric bypass surgery.

胃旁路术能迅速、持久地改善糖代谢，但其作用机制不清。本课题组前期研究发现，胃旁路术后解剖生理学发生改变的小肠其糖代谢发生重构（糖异生增强），并与肝糖输出减少密切相关，而研究发现小肠内甜味觉受体感知肠腔内营养素变化，对能量代谢和糖稳态具有重要的调节作用。结合上述研究，本课题组推测：胃旁路术后, 小肠糖代谢发生重构（糖异生作用增强），肠腔内营养素改变，进而通过小肠内甜味觉受体感知并上传信号，对术后肝糖输出产生了重要的调节作用。本课题拟以GK大鼠为动物模型，建立胃旁路术的手术模型十二指肠空肠旁路术（DJB），通过小肠灌注、细胞外微电极记录、扩展高胰岛素-正葡萄糖钳夹实验等技术，研究DJB术后食物经过的小肠糖代谢重构及甜味觉受体感知对肝糖输出的调节作用。本课题旨在探讨小肠糖代谢重构及甜味觉受体感知对胃旁路术后肝糖输出的调节作用，进一步揭示小肠在胃旁路术改善糖代谢中的作用和机制。

胃旁路术能迅速、持久地改善糖代谢，但其作用机制尚未完全阐明。本课题组前期研究发现，胃旁路术后解剖生理学发生改变的小肠其糖代谢发生重构（糖异生增强），并与肝糖输出减少密切相关，而研究发现小肠内甜味觉受体感知肠腔内营养素变化，对能量代谢和糖稳态具有重要的调节作用。本课题组结合前期研究，以GK大鼠为动物模型,建立了胃旁路术的手术模型十二指肠空肠旁路术（DJB）和袖状胃切除术（SG），研究发现 DJB术后小肠糖代谢发生重构（糖异生作用增强），同时小肠内甜味觉受体表达上调，参与了糖代谢的调节作用；同时本课题组联联合应用ITT、OGTT、HOMA-IR、PCT及 HIEC评估了SG术后胰岛素敏感性的改善作用。本研究进一步阐释了胃旁路术治疗2型糖尿病的机制，进一步揭示了小肠在胃旁路术改善糖代谢中的作用和机制。