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

Ann Surg. 2010 May;251(5):865-71. doi: 10.1097/SLA.0b013e3181d96e1f.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Dietary Sucrose / pharmacology
  • Duodenum / physiology
  • Glucose / pharmacology*
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Jejunum / physiology
  • Male
  • Mannitol / pharmacology
  • Ondansetron / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / physiology
  • Sodium-Glucose Transporter 1 / physiology*
  • Sucrose / pharmacology
  • Sweetening Agents / pharmacology*
  • Up-Regulation / physiology

Substances

  • Dietary Sucrose
  • Receptors, G-Protein-Coupled
  • Slc5a1 protein, rat
  • Sodium-Glucose Transporter 1
  • Sweetening Agents
  • Mannitol
  • Ondansetron
  • Sucrose
  • Glucose
  • Capsaicin