Putting the Hindgut Hypothesis to the Test in a Diabetic Zucker Rat Model
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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.
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.
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.
This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.
KeywordsMetabolic surgery Duodeno-jejunal bypass Diabetes Zucker rat
The authors thank Silke Hempel for the outstanding work in assistance with ELISA measurements. Moreover, we thank Anja Schmitt for her excellent work in the establishment of the GLP-1 immunostaining and Claudia Bravo and Monika Kolterjahn for their outstanding care of our animals.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed Consent Statement
Does not apply.
- 2.Mingrone G, Panunzi S, De Geaetano A, Guidone C, Ianconelli A, Nanni G. Bariatric–metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial - the lancet. Lancet 2015;386:964–973.Google Scholar
- 24.Peiris M, Aktar R, Raynel S, et al. Effects of obesity and gastric bypass surgery on nutrient sensors, endocrine cells, and mucosal innervation of the mouse colon. Nutrients. 2018;10: https://doi.org/10.3390/nu10101529.
- 30.Bhutta HY, Rajpal N, White W, et al. Effect of Roux-en-Y gastric bypass surgery on bile acid metabolism in normal and obese diabetic rats. PLoS One. 2015;10: https://doi.org/10.1371/journal.pone.0122273.