Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada.
Br J Surg. 2011 May;98(5):686-96. doi: 10.1002/bjs.7400. Epub 2011 Mar 4.
Obese patients with type II diabetes who undergo bariatric surgery revert to normal blood glucose and insulin levels, and develop a dramatic increase in insulin sensitivity. However, the mechanisms involved are unknown. This study characterized pancreatic islet and duodenojejunal enteroendocrine cells in normal mice and those with diabetes induced by a high-fat diet (HFD) following duodenojejunal bypass (DJB).
C57BL/6J mice, fed for 8 weeks either a normal diet (n = 10) or a HFD (n = 10) resulting in a hyperglycaemic state, underwent DJB (connection of the distal end of the jejunum to the distal stomach and direction of biliopancreatic secretions to the distal jejunum). Metabolic and immunohistological analyses were carried out on the pancreas and gastrointestinal tract.
A significant decrease in fasting blood glucose was observed in normal-DJB and HFD-DJB mice 1 week after the operation, with improved glucose tolerance at 4 weeks. There were no changes in pancreatic β-cell mass, but an increase in the ratio of α-cell to β-cell mass was observed in the DJB groups. Furthermore, the number of cells expressing Pdx-1, glucagon-like peptide 1, pancreatic polypeptide and synaptophysin was increased in the bypassed duodenum and/or gastrojejunum of the DJB groups.
Both normal and obese diabetic mice that underwent DJB displayed improved glucose tolerance and a reduction in fasting blood glucose, which mimicked findings in obese diabetic patients following bariatric surgery. The present data suggest that an increase in specific enteroendocrine cell populations may play a critical role in normalizing glucose homeostasis.
接受减重手术的 II 型糖尿病肥胖患者血糖和胰岛素水平恢复正常，并出现胰岛素敏感性的显著增加。然而，涉及的机制尚不清楚。本研究对正常小鼠和高脂饮食（HFD）诱导的糖尿病小鼠的胰岛和十二指肠空肠肠内分泌细胞进行了特征描述，这些小鼠接受了空肠空肠旁路术（DJB）。
C57BL/6J 小鼠分别用正常饮食（n=10）或高脂肪饮食（n=10）喂养 8 周，导致高血糖状态，然后进行 DJB（空肠远端与胃远端连接，胆汁胰液流向空肠远端）。对胰腺和胃肠道进行代谢和免疫组织学分析。
正常-DJB 和 HFD-DJB 小鼠在手术后 1 周空腹血糖显著下降，4 周时葡萄糖耐量改善。β细胞质量无变化，但 DJB 组的α细胞与β细胞质量比增加。此外，DJB 组旁路空肠和/或胃空肠中表达 Pdx-1、胰高血糖素样肽 1、胰多肽和突触素的细胞数量增加。
接受 DJB 的正常和肥胖糖尿病小鼠均表现出改善的葡萄糖耐量和空腹血糖降低，类似于肥胖糖尿病患者接受减重手术后的发现。本研究数据表明，特定肠内分泌细胞群体的增加可能在血糖稳态正常化中发挥关键作用。
