Effects of Metformin and Sitagliptin Monotherapy on Expression of
Intestinal and Renal Sweet Taste Receptors and Glucose Transporters in a Rat
Model of Type 2 Diabetes
Minchun Zhang‡
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Rilu Feng‡
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Jiang Yue‡
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Cheng Qian
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Mei Yang
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Wei Liu
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
,
Christopher K. Rayner
2
Centre of Research Excellence in Translating Nutritional Science to
Good Health, University of Adelaide, Adelaide, Australia
3
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital,
Adelaide, Australia
,
Jing Ma
1
Department of Endocrinology and Metabolism, Renji Hospital, School of
Medicine, Shanghai Jiaotong University, Shanghai, China
› Author AffiliationsFunding: This work was supported by National Natural
Science Foundation of China (NSFC 81670728), Shanghai Pujiang Program
(2019PJD027), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine
Grant Support (20181807) and Clinical research funding in Renji Hospital
affiliated to Shanghai Jiaotong University
(PYZY16–020).
Disordered 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.
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