Neurogastroenterology

Expression of taste molecules in the upper gastrointestinal tract in humans with and without type 2 diabetes

R L Young^1,3,4, K Sutherland^2,3, N Pezos^2,3, S M Brierley^2,3, M Horowitz^1,4, C K Rayner^1,4, L A Blackshaw^1,2,3,4

¹ Discipline of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia
² Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia
³ Nerve-Gut Research Laboratory, Hanson Institute, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
⁴ National Health and Medical Research Council of Australia Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, Australia

Dr R L Young, Nerve-Gut Research Laboratory, Level 1 Hanson Institute, Frome Rd, Adelaide SA 5000, Australia; richard.young{at}adelaide.edu.au

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 -gustducin (G_gust) 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, G_gust and TRPM5 were quantified in gastrointestinal mucosal biopsies from subjects with and without type 2 diabetes; immunohistochemistry was used to locate G_gust. Effects of luminal glucose on jejunal expression of taste molecules were also quantified in mice.

Results: T1R2, T1R3, G_gust and TRPM5 were preferentially expressed in the proximal small intestine in humans, with immunolabelling for G_gust localised to solitary cells dispersed throughout the duodenal villous epithelium. Expression of T1R2, T1R3, TRPM5 (all p<0.05) and G_gust (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.

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