Rapid upregulation of sodium-glucose transporter SGLT1 in response to intestinal sweet taste stimulation.
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.


BACKGROUND
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.
Stearns
Adam T
AT
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Balakrishnan
Anita
A
Rhoads
David B
DB
Tavakkolizadeh
Ali
A
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D019422:Dietary Sucrose / Q000494:pharmacology; D004386:Duodenum / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000502:physiology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology*; D013395:Sucrose / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology*; D015854:Up-Regulation / Q000502:physiology
D019422:Dietary Sucrose; D043562:Receptors, G-Protein-Coupled; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D013549:Sweetening Agents; D008353:Mannitol; D017294:Ondansetron; D013395:Sucrose; D005947:Glucose; D002211:Capsaicin
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