Gastroenterology

Gastroenterology

Volume 150, Issue 2, February 2016, Pages 454-464.e9
Gastroenterology

Original Research
Full Report: Basic and Translational—Alimentary Tract
Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

https://doi.org/10.1053/j.gastro.2015.10.009Get rights and content

Background & Aims

Bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type 2 diabetes in obese individuals. Alimentary glucose absorption and intestinal disposal of blood glucose have not been directly compared between individuals or animals that underwent RYGB vs VSG. We evaluated in rats and humans how the gut epithelium adapts after surgery and the consequences on alimentary glucose absorption and intestinal disposal of blood glucose.

Methods

Obese male rats underwent RYGB, VSG, or sham (control) operations. We collected intestine segments from all rats; we performed histologic analyses and measured levels of messenger RNAs encoding the sugar transporters SGLT1, GLUT1, GLUT2, GLUT3, GLUT4, and GLUT5. Glucose transport and consumption were assayed using ex vivo jejunal loops. Histologic analyses were also performed on Roux limb sections from patients who underwent RYGB 1−5 years after surgery. Roux limb glucose consumption was assayed after surgery by positron emission and computed tomography imaging.

Results

In rats and humans that underwent RYGB, the Roux limb became hyperplasic, with an increased number of incretin-producing cells compared with the corresponding jejunal segment of controls. Furthermore, expression of sugar transporters and hypoxia-related genes increased and the nonintestinal glucose transporter GLUT1 appeared at the basolateral membrane of enterocytes. Ingested and circulating glucose was trapped within the intestinal epithelial cells of rats and humans that underwent RYGB. By contrast, there was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose was reduced and density of endocrine cells secreting glucagon-like peptide-1 increased.

Conclusions

The intestine adapts differently to RYGB vs VSG. RYGB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.

Section snippets

Materials and Methods

See Supplementary Material for detailed descriptions.

Roux-en-Y Gastric Bypass Quickly Induces Hypertrophy of the Alimentary Roux Limb

We studied early events after RYGB surgery either in a diet-induced obese rat model (Supplementary Text 1 and Supplementary Figures 1 and 2). As soon as 2 weeks after surgery, the alimentary RL was hypertrophic and displayed a dramatic increase in its diameter compared with that of the biliopancreatic limb (BPL) or with the corresponding jejunal segment of sham-operated rats (Figure 1A). The villus height and crypt depth of the RL were increased, leading to a thicker mucosa, and no modification

Discussion

In this study, using diet-induced obese rats, we directly compared the impact of 2 bariatric procedures on the glucose transport capacity of the intestine. We identified 2 distinct but rapid adaptations affecting intestinal morphology and glucose handling (Figure 7). In response to VSG, glucose transport capacity is reduced and density of cells secreting GLP1 is increased. In response to RYGB, the intestine became hyperplasic increasing de facto the number of GLP1-secreting cells but, more

Acknowledgments

The authors would like to thank the team of Nathalie Kapel at Department of Functional coprology, APHP for stool analyses; Prof D. Le Guludec, who is responsible for FRIM imaging platform and chief of the nuclear physic department; O. Thibaudeau and S. Ameur for help in histologic experiments; V. Descatoire for help in histologic analyses; L. Aline for technical help; and J. Le Beyec, H. Duboc and S. Ledoux for comments. Maude Le Gall thanks L. Arnaud for constant support.

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by French Minister of Higher Education and Research, INSERM and University Paris Diderot.

    Author names in bold designate shared co-first authorship.

    §

    Authors share co-senior authorship.

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