Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport - PubMed (original) (raw)

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

Adam T Stearns et al. Am J Physiol Gastrointest Liver Physiol. 2009 Nov.

Abstract

Roux-en-Y gastric bypass (RYGB) has become the gold-standard bariatric procedure, partly because of the rapid resolution of accompanying diabetes. There is increasing evidence this is mediated by duodenal exclusion. We hypothesize that duodenal exclusion suppresses intestinal Na(+)/glucose cotransporter SGLT1-mediated glucose transport, improving glucose handling, and aimed to test this in a rodent RYGB model. Sprague-Dawley rats underwent sham procedure or duodenal exclusion by RYGB (10 cm Roux, 16 cm biliopancreatic limbs). Animals were maintained for 3 wk on a Western diet, before harvest at 10 AM, 4 PM, and 10 PM. Sections were taken from each limb for hematoxylin and eosin staining, and morphological assessment was performed. Functional glucose uptake studies, along with Western blotting and quantitative PCR, were performed on Roux limb. Histology showed morphometric changes in Roux and common limbs, with increase in villus height and crypt depth compared with BP and sham jejunum. Despite this, glucose transport was reduced by up to 68% (P < 0.001) in the Roux limb compared with sham jejunum. Normal diurnal rhythms in glucose uptake were ablated. This occurred at a posttranscriptional level, with little change in message but appearance of different weight species of Sglt1 on Western blotting. We have shown duodenal exclusion significantly influences both intestinal structure and glucose transport function, with glucose absorptive capacity reduced after RYGB. This provides a novel mechanistic explanation for some of the antidiabetic effects of RYGB.

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Figures

Fig. 1.

Fig. 1.

A: Transection of the stomach between hemostats, with the gastric pouch (GP) and gastric remnant (R). The gastric pouch includes glandular mucosa, with the junction between the glandular and squamous mucosa indicated with a dashed line. The vagus has been mobilized and preserved along with the left and right gastric vessels in the lesser curve (white arrow). B: final reconstruction, with a 10-cm Roux limb (yellow arrows) draining the gastric pouch before continuing as the common channel (black arrows). The Roux limb is joined by the 16-cm biliopancreatic (BP) limb, identified with gray arrows. C: schematic diagram showing the orthotopic position of BP, Roux, and common (Comm) limbs compared with the ligament of Trietz, and compared with sham animals. Sections for histology were taken from the gray shaded regions: these were all less than 8 cm from the orthotopic position of the sham jejunum.

Fig. 2.

Fig. 2.

A: Daily weights for each of the sham and Roux-en-Y gastric bypass (RYGB) animals, where weight is given relative to the weight on the morning of surgery. Sham animals maintained their weight postoperatively until resumption of solid diet (indicated by the vertical dotted line); at this point, they rapidly gained weight. RYGB animals continued to lose weight until the 7th postoperative day; they remained significantly lighter (P < 0.05) than sham animals throughout the postoperative course. B: whereas sham animals ate relatively constant daily rations of food, RYGB animals initially ate very little. This rapidly increased, until by the 11th postoperative night food consumption was the same between operative arms. *P < 0.05 compared with shams.

Fig. 3.

Fig. 3.

Summary of the morphological comparisons between sham jejunum and the differing limbs in RYGB. A: villus height, with Roux and common limbs significantly longer than both sham and BP limbs. B: mean enterocyte diameter, with no difference between the limbs, suggesting differences in length are due to enterocyte number rather than volume. C: crypt depth, increased depth in all limbs after RYGB compared with shams. This was partly due to an increase in crypt column cell count (D). Lastly, Roux and common limbs, but not BP limb, had increased numbers of goblet cells in both villus (E) and crypt (F) compared with shams. Compared with sham: *P < 0.05; **P < 0.01; ***P < 0.001.

Fig. 4.

Fig. 4.

A: representative photomicrographs of intestinal sections of sham jejunum (Sh), Roux (Rx), BP, and common (Com) limb. The variations in villus height can be clearly seen, with Roux and common limb villi of greater length than those of sham jejunum and BP limb. B: representative crypts, again with deeper crypts in Roux and common limbs compared with sham jejunum and BP limbs. There was a shift in enterocyte lineage, with an increase in goblet cells in villi in Roux and common limbs compared with sham and BP limbs. This is seen in representative sections from common limb and sham jejunum cut perpendicular to sheets of midvillus enterocytes, as can be seen by the visible tight junctions between enterocytes (black arrowheads). In common limb villi, there is a much greater abundance of goblet cells than in sham jejunum. Scale bars: A, 200 μm; B and C, 50 μm.

Fig. 5.

Fig. 5.

A: intestinal glucose transport capacity by time. Glucose uptake capacity in sham jejunum showed a normal diurnal rhythm, peaking at hours after lights on (HALO)-9 just prior to onset of feeding. This was completely abolished after RYGB. Glucose uptake capacity was significantly reduced in RYGB animals at all 3 times (***P < 0.001 compared with shams). B: the assay repeated in the presence of 20 μm phloridzin, confirming measured glucose transport represents Sglt1.

Fig. 6.

Fig. 6.

A: Sglt1 transcriptional data, expressed relative to Actin and indexed to a standard. Both RYGB and sham animals show an expected diurnal rhythm, but it is blunted in RYGB, with increased basal expression (compared with shams: **P < 0.01; ***P < 0.001). B: a representative Western blot for Roux and sham tissue harvested at HALO-15; in sham tissue, there is a single band seen at 73 kDa. After RYGB, there are additional species seen at 67 and 88 kDa. C: a representative Western blot image for sham jejunum vs. Roux, BP, or common limbs. Note, the samples from RYGB animals are taken from the same 3 animals for each of the Roux, BP, or common channels. In RYGB animals, deglycosylated Sglt1 is seen in all 3 limbs, regardless of nutrient or BP exposure. However, the heavy species of Sglt1 at 88 kDa is more pronounced in the Roux limb compared with those exposed to BP secretions.

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