在糖尿病 Zucker 大鼠模型中检验后肠假说。

Putting the Hindgut Hypothesis to the Test in a Diabetic Zucker Rat Model.

机构信息

Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.

Faculty of Medicine, Institute of Pathology, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.

出版信息

Obes Surg. 2019 Dec;29(12):4000-4007. doi: 10.1007/s11695-019-04079-w.

DOI:10.1007/s11695-019-04079-w

PMID:31367988

Abstract

BACKGROUND

The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus.

METHODS

Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly.

RESULTS

In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups.

CONCLUSION

This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.

摘要

背景

后肠假说假设代谢手术后，后肠刺激的差异在改善糖尿病方面起着关键作用。我们使用两种策略将后肠从肠道连续性中分离出来，以分析其对糖尿病的影响。

方法

在 3 组 9 周龄 Zucker 糖尿病肥胖大鼠中进行回肠-空肠吻合术（DJOS），同时排除三分之一的总肠长度。在第 1 组中，没有对肠道进行进一步改变。第 2 组接受额外的回肠切除（IE）。第 3 组接受额外的 50%回肠切除术和侧侧回盲吻合术（IR）。手术后 1、2 和 4 个月，进行空腹血糖水平、口服葡萄糖耐量试验（OGTT）和葡萄糖刺激激素分析，并比较胆汁酸血水平。每周记录体重。

结果

与 DJOS 相比，IR 或 IE 并没有损害葡萄糖控制。相反，只有 IR 可以在 4 个月内维持术前的血糖值。各组之间的体重没有显著差异。证实有效的回肠分流，DJOS 组的胆汁酸血水平明显高于 IR 和 IE 组（p=0.0025 和 p=0.0047）。手术干预在任何时间点对 GLP-1 水平都没有影响（ANOVA p>0.05 所有）。胰岛素分泌在所有组中均得到保留。