Sucralose can improve glucose tolerance and upregulate expression of sweet taste receptors and glucose transporters in an obese rat model

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: GLP-1; Intragastric glucose tolerance test; Non-nutritive sweeteners; SGLT-1; Sweet taste receptors.