T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways
| Autor: | Timothy F. Osborne, Elnaz Karimian Azari, Paula P Veldhuis, Traci E. LaMoia, Richard E. Pratley, Veronika Vargova, Kathleen R. Smith, Juan Pablo Arnoletti, Sebastian G. de la Fuente, Katalin Karolyi, Tania Hussain, George Kyriazis |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
EEC enteroendocrine cells Male Isc short-circuit current Enteroendocrine cell Glucose homeostasis Receptors G-Protein-Coupled Papp apparent permeability coefficient Mice 0302 clinical medicine Glucagon-Like Peptide 2 Intestinal Mucosa Receptor 3-OMG 3-O-methylglucose Mice Knockout biology Chemistry digestive oral and skin physiology WAT white adipose tissue Peptide secretion GI gastrointestinal HSD high sucrose diet humanities Cell biology Jejunum Taste GLP-1 and GLP-2 glucagon-like peptides-1 and -2 Original Article Female IP intraperitoneal T1R2 HPV hepatic portal vein Signal Transduction lcsh:Internal medicine KO knock out STRs sweet taste receptors Enteroendocrine Cells 030209 endocrinology & metabolism Sweet taste receptors 03 medical and health sciences Downregulation and upregulation PYY peptide YY Animals Secretion TTX tetrodotoxin lcsh:RC31-1245 Molecular Biology Gcg pro-glucagon Glucose transporter Biological Transport Cell Biology IG.GTT intragastric glucose tolerance test Apical membrane Mice Inbred C57BL 030104 developmental biology Glucose Intestinal Absorption biology.protein GLUT2 Energy Metabolism GLP-2 TER tissue trans-epithelial resistance |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 17, Iss, Pp 98-111 (2018) |
| ISSN: | 2212-8778 |
| Popis: | Objective Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Methods Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. Results STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Conclusions Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars. Highlights • The intestinal T1R2 receptor enhances glucose absorption in vivo and ex vivo. • Pharmacological inhibition of STRs reduces glucose flux in human intestinal preparations. • T1R2 regulates glucose absorption dependent on GLUT2 activity in enterocytes. • GLP-2 mediates the effects of T1R2 signaling through activation of enteric neurons. • High sucrose diet rapidly downregulates STRs leading to reduced glucose absorption. |
| Databáze: | OpenAIRE |
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