Journal
ANNALS OF SURGERY
Volume 251, Issue 5, Pages 865-871Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0b013e3181d96e1f
Keywords
-
Categories
Funding
- National Institute of Health [5 R01 DK047326]
- Harvard Clinical Nutrition Center [P30-DK040561]
- American Diabetes Association [7-05-RA-121]
- Berkeley Fellowship
- George Herbert Hunt Travelling Fellowship
- Nutricia Foundation Fellowship
Ask authors/readers for more resources
Objective: We set out to examine the short-term regulation of the intestinal sodium/glucose cotransporter SGLT1 by its substrate glucose and sweet taste analogs. Summary Background Data: Intestinal SGLT1 is a putative target for antidiabetic therapy; however, its physiological regulation is incompletely understood, limiting its application as a pharmacological target. While it is clearly regulated by dietary composition over a period of days, its short-term regulation by nutrients is unknown. Methods: Sprague-Dawley rats were anesthetized, and the duodenum cannulated. D-glucose, D-fructose, saccharin, D-mannitol, and water were infused for 3 hours, before harvest of proximal jejunum for SGLT1 analysis with Western blotting and quantitative polymerase chain reaction. In further experiments, the receptor region was identified by D-glucose infusion of isolated regions. Lastly, the vagus was de-afferented with capsaicin, and 5HT3-receptor activation of vagal afferents inhibited using ondansetron, before repeating experiments using water or D-glucose infusion. Results: Infusion of D-glucose led to 2.9-fold up-regulation in SGLT1 compared with water or iso-osmotic D-mannitol; this effect was replicated by D-fructose or saccharin. This response was strongest following isolated infusions of duodenum and proximal jejunum, with a blunted effect distally; topography matched the expression profile of sweet taste receptor T1R2/T1R3. The reflex was abolished by capsaicin pretreatment, and blunted by ondansetron. Conclusions: The agonist response implicates the luminal-based sweet-taste receptor T1R2/T1R3, with the reflex apparently involving vagal afferents. The proximal nature of the sensor coincides with the excluded biliopancreatic limb in Roux-en-Y gastric bypass, and this may provide a novel explanation for the antidiabetic effect of this procedure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available