Objective: Nutrient feedback from the small intestine modulates upper gastrointestinal function and energy intake; however, the molecular mechanism of nutrient detection is unknown. In the tongue, sugars are detected via taste T1R2 and T1R3 receptors and signalled via the taste G-protein α-gustducin (Gαgust) and the transient receptor potential ion channel, TRPM5. These taste molecules are also present in the rodent small intestine, and may regulate gastrointestinal function.
Subjects and methods: Absolute transcript levels for T1R2, T1R3, Gαgust and TRPM5 were quantified in gastrointestinal mucosal biopsies from subjects with and without type 2 diabetes; immunohistochemistry was used to locate Gαgust. Effects of luminal glucose on jejunal expression of taste molecules were also quantified in mice.
Results: T1R2, T1R3, Gαgust and TRPM5 were preferentially expressed in the proximal small intestine in humans, with immunolabelling for Gαgust localised to solitary cells dispersed throughout the duodenal villous epithelium. Expression of T1R2, T1R3, TRPM5 (all p<0.05) and Gαgust (p<0.001) inversely correlated with blood glucose concentration in type 2 diabetes subjects but, as a group, did not differ from control subjects. Transcript levels of T1R2 were reduced by 84% following jejunal glucose perfusion in mice (p<0.05).
Conclusions: Taste molecules are expressed in nutrient detection regions of the proximal small intestine in humans, consistent with a role in “tasting”. This taste molecule expression is decreased in diabetic subjects with elevated blood glucose concentration, and decreased by luminal glucose in mice, indicating that intestinal “taste” signalling is under dynamic metabolic and luminal control.
Statistics from Altmetric.com
RLY and KS contributed equally to this work.
Funding: This work was supported by funds received from the Royal Adelaide Hospital, Institute of Medical & Veterinary Sciences and the University of Adelaide. Richard L. Young was supported by a National Health and Medical Research Council of Australia (NHMRC) Centre for Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes Postdoctoral Fellowship. Stuart M Brierley was supported by an NHMRC Australian Biomedical Fellowship. L. Ashley Blackshaw was supported by an NHMRC Senior Research Fellowship.
Competing interests: None.
Ethics approval: Human studies were approved by the Human Research Ethics Committee of the Royal Adelaide Hospital, Adelaide, Australia, and each subject gave written, informed consent. Animal studies were performed in accordance with the guidelines of the Animal Ethics Committee of the Institute of Medical & Veterinary Science (Adelaide, Australia) and the University of Adelaide.
Preliminary accounts of this work were presented at the Digestive Disease Week meetings of the American Gastroenterological Association in Washington, DC (2007)28 and San Diego, CA (2008).43
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.