title: Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport.
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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Stearns
authors.forename: Anita
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Ali
authors.initials: A
authors.lastname: Tavakkolizadeh
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002452:Cell Count; D002940:Circadian Rhythm / Q000502:physiology; D004435:Eating / Q000502:physiology; D020895:Enterocytes / Q000473:pathology; D015390:Gastric Bypass; D015870:Gene Expression / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D020397:Goblet Cells / Q000473:pathology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D008297:Male; D008970:Molecular Weight; D010695:Phlorhizin / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D010695:Phlorhizin; D005947:Glucose