title: Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption.
abstract: Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners, such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600-fold>glucose). This, combined with oral bioavailability of T1R2-T1R3 and the understanding that artificial sweetener-induced receptor activation evokes GLP-2 release (thus leading to increased SGLT1 expression and mucosal growth), make this receptor a suitable target for dietary manipulation.
authors.affiliation: Epithelial Function and Development Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: A W
authors.initials: AW
authors.lastname: Moran
authors.affiliation: Epithelial Function and Development Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Al-Rammahi
authors.affiliation: Epithelial Function and Development Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Pancosma SA, 1218 Geneva, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Bravo
authors.affiliation: Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Calsamiglia
authors.affiliation: Epithelial Function and Development Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom. Electronic address: spsb@liverpool.ac.uk.
authors.forename: S P
authors.initials: SP
authors.lastname: Shirazi-Beechey
mesh_terms: D000821:Animal Feed; D000818:Animals; D002417:Cattle; D004032:Diet / Q000662:veterinary; D053767:Glucagon-Like Peptide 2 / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012418:Ruminants / Q000378:metabolism; D012756:Sheep; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D013549:Sweetening Agents / Q000008:administration & dosage*; D013557:Switzerland; D013649:Taste; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053767:Glucagon-Like Peptide 2; D043562:Receptors, G-Protein-Coupled; D051269:Sodium-Glucose Transporter 1; D013549:Sweetening Agents; C431926:taste receptors, type 1; C075192:gustducin; D015293:Transducin; D005947:Glucose
keywords: glucose absorption; intestine; ruminant; taste 1 receptor 2; taste 1 receptor 3