Sucralose can improve glucose tolerance and upregulate expression of sweet taste receptors and glucose transporters in a

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Sucralose can improve glucose tolerance and upregulate expression of sweet taste receptors and glucose transporters in an obese rat model Cheng Qian1 · Yicheng Qi1 · Rilu Feng1 · Mei Yang1 · Minchun Zhang1 · Wei Liu1 · Christopher K. Rayner3,4 · Jing Ma1,2 Received: 6 March 2020 / Accepted: 24 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Objectives  Non-nutritive sweeteners (NNS) are widely used as replacements for table sugar in beverages and dessert. However, the metabolic effects of NNS remain controversial. This study aimed to investigate the effects of various sucralose loads on glucose metabolism and expression of sweet taste receptors (STR) and glucose transporters in a high-fat diet (HFD) rats. Methods  Four-week-old male Sprague Dawley rats were fed a HFD for 8 weeks, then randomly divided into eight groups (6 in each group). All were gavaged with either saline, sucralose (0.54 mM or 0.78 mM), or sucrose (324 mM) with/without gurmarin, a sweet taste inhibitor, for 4 weeks, followed by an intragastric glucose tolerance test (IGGTT) with blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) measurements. In the following week, the rats were sacrificed and the small intestine was removed for measurement of sweet taste receptor and glucose transporter expression by quantitative Reverse Transcription-Polymerase Chain Reaction. Results  In HFD rats, blood glucose levels were decreased at 30, 60, and 120 min during the IGGTT after 4 weeks supplementation with 0.78 mM sucralose. TIR3 expression was increased in the duodenum and TIR2 was increased in the ileum after 324 mM sucrose supplementation. T1R3 expression was increased after 0.54 mM and 0.78 mM sucralose in the ileum, but there was no change in the expression of TIRs in the duodenum after sucralose treatments. SGLT-1 expression was increased after both 0.78 mM sucralose and 324 mM sucrose in the ileum, and only increased in the duodenum after 324 mM sucrose supplementation. Conclusions  The effects of sucralose on glucose metabolism in HFD rats are dose-dependent and related to enhanced expression of sweet taste receptors and glucose transporters. Further studies are needed to clarify the molecular mechanisms involved. Keywords  Non-nutritive sweeteners · Intragastric glucose tolerance test · GLP-1 · Sweet taste receptors · SGLT-1

Introduction Cheng Qian and Yicheng Qi contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0039​4-020-02375​-1) contains supplementary material, which is available to authorized users.

Diabetes, a growing worldwide challenge, is associated with increased consumption of sugars, particularly sucrose [1]. Non-nutritive sweeteners (NNS) mimic the taste of sucrose and were considered useful as substitutes to reduce energy

* Jing Ma [email protected]

2



China Hospital Development Institute, Shanghai Jiao Tong University, Shanghai, China

Christopher