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Horm Metab Res 2020; 52(05): 329-335
DOI: 10.1055/a-1135-9031
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

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 Affiliations Funding: 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).
Further Information

Publication History

received 31 May 2019

accepted 03 March 2020

Publication Date:
06 April 2020 (online)

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Abstract

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.

Key words

glucose transporter proteins - metformin - sitagliptin - sweet taste receptors
 

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