Volume 23, Issue 3, Pages 547-553 (March 2016) Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake  Gregory Baud, Mehdi Daoudi, Thomas Hubert, Violeta Raverdy, Marie Pigeyre, Erik Hervieux, Magalie Devienne, Mohamed Ghunaim, Caroline Bonner, Audrey Quenon, Pascal Pigny, André Klein, Julie Kerr-Conte, Valery Gmyr, Robert Caiazzo, François Pattou  Cell Metabolism  Volume 23, Issue 3, Pages 547-553 (March 2016) DOI: 10.1016/j.cmet.2016.01.018 Copyright © 2016 Elsevier Inc. Terms and Conditions

Cell Metabolism 2016 23, 547-553DOI: (10.1016/j.cmet.2016.01.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Postprandial Glucose Homeostasis following RYGB during the Progression of a Mixed Meal through AL and CL in Minipigs (A) Schematic representation of the progression of a mixed meal (MM) in the AL (red) and in the CL (blue) following clamp removal (n = 5). (B–D) Blood glucose (B), plasma insulin (C), and plasma GLP-1 (D) concentrations in response to the progression of the meal in the AL (red circles) and in the CL (blue circles). (E) Schematic representation of the progression of a MM in the AL (red), in the proximal CL (purple), and in the distal CL (blue) (n = 4) following the sequential removal of the clamps. (F–H) Blood glucose (F), plasma insulin (G), and plasma GLP-1 (H) concentrations in response to the progression of the meal in the AL (red circles), in the proximal CL (purple circles), and in the distal CL (blue circles). One-way ANOVA test for repeated-measures and Bonferroni post-hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 versus baseline. All values are mean ± SEM. Cell Metabolism 2016 23, 547-553DOI: (10.1016/j.cmet.2016.01.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 Addition of Bile Restores Active Sodium-Glucose Cotransport in the AL in Minipigs (A and B) Plasma D-xylose concentrations (A) and blood glucose concentrations (B) following the instillation of glucose and D-xylose in the AL (open circles; n = 4), or glucose, D-xylose, and phlorizin (black circles; n = 4), before and after the addition of bile (arrow). One-way ANOVA test for repeated measures and Bonferroni post-hoc test; ∗p < 0.05, ∗∗∗p < 0.001 versus baseline. All values are mean ± SEM. (C) mRNA levels of intestinal glucose transporters SGLT1, GLUT1, GLUT2, GLUT3, and GLUT5 were evaluated in the three intestinal limbs (AL, BL, and CL) by real-time qPCR and normalized to ACTG (encoding for actin gamma 1) as internal control (n = 7); CL set to 1. Cell Metabolism 2016 23, 547-553DOI: (10.1016/j.cmet.2016.01.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 Effect of Endoluminal Sodium Content in the AL on Glucose and D-Xylose Intestinal Uptake in Minipigs (A) Sodium (Na) content in the three intestinal limbs of RYGB (n = 5). One-way ANOVA test and Bonferroni post-hoc test; ∗p < 0.05, ∗∗∗p < 0.001. (B and C) Plasma D-xylose (B) and blood glucose concentrations (C) before and after injection of NaCl in the AL instilled with glucose and D-xylose (n = 4). One-way ANOVA test for repeated-measures and Bonferroni post-hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 versus baseline. All values are mean ± SEM. (D) Plasma D-xylose concentrations in response to a MM without (open circles) or with (blue circles) 2 g of sodium (n = 5, paired). Two-way ANOVA and Bonferroni post-hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001; all values are mean ± SEM. The gray area represents the results in healthy control minipigs (n = 28). (E) Box plot showing the area under the curve of D-xylose concentrations in response to MM without (open) or with (blue) 2 g of sodium (n = 5, paired). Paired t test; ∗p < 0.05. (F) Blood glucose concentrations in response to a MM without (open circles) or with (blue circles) 2 g of sodium (n = 5, paired). Two-way ANOVA and Bonferroni post-hoc test; ∗p < 0.05; all values are mean ± SEM. The gray area represents the results in healthy control minipigs (n = 28). (G) Box plot showing the area under the curve of blood glucose concentrations in response to a MM without (open) or with (blue) 2 g of sodium (n = 5, paired). Paired t test; ∗p < 0.05. Cell Metabolism 2016 23, 547-553DOI: (10.1016/j.cmet.2016.01.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 4 Changes in Glucose and D-Xylose Intestinal Uptake after RYGB in Humans (A) Plasma D-xylose concentrations in response to a MM before (open circles) and after (red circles) RYGB in human (n = 9, paired). Two-way ANOVA and Bonferroni post-hoc test; ∗∗p < 0.01, ∗∗∗p < 0.001. All values are mean ± SEM. (B) Box plot showing the area under the curve of plasma D-xylose concentrations in response to a MM before (open) and after (red) RYGB (n = 9, paired). Paired t test; ∗p < 0.05. (C) Blood glucose concentrations in response to a MM before (open circles) and after (red circles) RYGB in human (n = 9, paired). Two-way ANOVA and Bonferroni post-hoc test; ∗∗∗p < 0.001. All values are mean ± SEM. (D) Box plot showing the area under the curve of blood glucose concentrations in response to a MM before (open) and after (red) RYGB (n = 9, paired). Paired t test; ∗p < 0.05. (E and F) Plasma insulin (E) and plasma GLP-1 (F) concentrations in response to a MM before (open circles) and after (red circles) RYGB in human (n = 9, paired). Two-way ANOVA and Bonferroni post-hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. All values are mean ± SEM. Cell Metabolism 2016 23, 547-553DOI: (10.1016/j.cmet.2016.01.018) Copyright © 2016 Elsevier Inc. Terms and Conditions