Do Compensatory Changes Occur in Intestinal Glucose Transport Following Gastric Bypass in Type 2, Diabetic Rats

Abstract

Although there is a considerable amount of evidence in the literature showing that Rouen‐en‐Y‐Gastric Bypass (RYGB) in particular, is very effective in resolving Type 2, Diabetes (T2D), a very fundamental question that has not yet been addressed is how transmural glucose transport is modified across the newly configured anatomy of the upper intestinal segments following RYGB? Thus, the objective of the study was to examine potential adaptations in glucose transport across the Roux Limb and distal ileum of ZDF (Zucker Diabetic Fatty) and ZLC (Zucker Lean Control) rats following RYGBUnidirectional glucose fluxes were measured in Ussing chambers under symmetrical, short‐circuited conditions in vitro ~ 10 weeks following the surgical procedure. Segments that were removed included ~ 4 cm of proximal Roux Limb measured from the stomach pouch insertion point; a segment ~ 4 cm at the location measured 35 cm from the ileo‐caecal valve and representing the “predestined” Roux limb in control rats; and a similar size segment immediately proximal to the ileocaecal valve which is the most distal ileum that is not reconfigured in any animal. Using radio‐labeled [14C]‐3‐0‐methylglucose, unidirectional fluxes of glucose were measured across paired adjacent tissues from the mucosal to serosal bath, Jms (absorptive component) and in the opposite direction from serosal to mucosal, Jsm (secretory component) over a 45 min time period. The overall net transport of glucose (Jnet) was determined by subtracting the two unidirectional fluxes. Both the short‐circuit current (Isc) and the transepithelial voltage generated by the tissue is recorded at 15 min intervals and tissue conductance (GT) is calculated from these electrical parameters using Ohm's Law.Major changes in glucose fluxes occurred in obese ZDF/RYGB rats compared to ZDF controls in both of the intestinal segments examined. The unidirectional glucose fluxes are dramatically reduced in RYGB rats and the direction of net glucose transport is reversed across the Roux Limb. It is also notable that tissue conductance of the Roux Limb is reduced by ~ 48% (from GT of 12.0 ± 2.2 mS.cm‐2 in n=8 “predestined” Roux Limb tissues to GT = 6.2 ± 1.3 mS.cm‐2, n=6 Roux Limb tissues) consistent with the lowering (~40% in Jms and ~95% in Jsm) of both unidirectional glucose fluxes indicating an adaptive change in overall tissue permeability. A significant reduction (~82%) occurred in net glucose absorption across the ZDF/RYGB distal ileum (which is not surgically re‐configured) largely via a 64% reduction in Jms. The “predestined” Roux limb of the lean ZLC rats supports a very robust net absorption of glucose that is completely abolished in the reconfigured ZLC/RYGB limb and the unidirectional fluxes were greatly diminished (~90% in Jms and ~70% in Jsm) as was GT from 14.5 ± 2.8 mS.cm‐2 in n=4 “predestined” Roux Limb tissues to GT = 8.0 ± 1.1 mS.cm‐2, n=4 Roux Limb tissues) which is a very similar response to that observed in the obese ZDF rats. There were also major alterations in glucose fluxes across the distal ileum of the lean ZLC/RYGB rats which supported a robust net secretion compared to a net absorption in the lean ZLC controls and no change in GT. To our knowledge, these are the first measurements of intestinal glucose transport in ZDF rats with/without RYGB. In conclusion, we are proposing that altered intestinal handling of glucose may be contributing to the resolution of T2D post RYGB.Support or Funding InformationDK089000