AbstractDisordered intestinal sweet taste receptors (STRs) are implicated in glucose
homeostasis by involving in incretin secretion and glucose absorption. However,
the effects of antidiabetic medications on STRs, downstream molecules, and
glucose transporters expression are unknown. In our study, ZDF rats
(n=24) were randomly treated by metformin (MET,
215.15 mg/kg), sitagliptin (SIT, 10.76 mg/kg),
or saline for 4 weeks. Fasting blood glucose and insulin levels were measured,
and HOMA-IR and QUICKI index were calculated. One week later, we detected
relative mRNA expression of T1R2/T1R3, α-gustducin, TRPM5 and
glucose transporters including SGLT1, SGLT2, and GLUT2 in the small intestine
and kidney. We found that though both metformin and sitagliptin effectively
decreased fasting blood glucose, only metformin improved HOMA-IR and QUICKI
(p<0.05). MRNA levels of STRs and sweet taste molecules in duodenum and
jejunum were not different among three groups, but those in ileum were
dramatically upregulated after SIT (vs. MET p<0.05; vs. CON
p<0.01). SGLT1 and GLUT2 in ileum were markedly increased after SIT
(p<0.01). In the kidney, expression of SGLT2 and GLUT2 were
downregulated in both SIT and MET group (p<0.05). In conclusion,
metformin and sitagliptin exerted different effects on expression of STRs and
glucose transporters in the gut and kidney. STRs, downstream molecules, and
glucose transporters in distal small intestinal were sensitively increased in
response to sitagliptin than metformin treatment. Renal glucose transporters
were downregulated after metformin and sitagliptin treatment.
Secretion of Gut Hormones and Expression of Sweet Taste Receptors and Glucose Transporters in a Rat Model of Obesity
